Journal articles: 'Syngeneic model'

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Filho, Ivo P. Torres, Beryl Hartley-Asp, and Per Borgström. "Quantitative Angiogenesis in a Syngeneic Tumor Spheroid Model." Microvascular Research 49, no. 2 (March 1995): 212–26. http://dx.doi.org/10.1006/mvre.1995.1017.

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Chen, Yi-Fen, Kuo-Wei Chang, I.-Ting Yang, Hsi-Feng Tu, and Shu-Chun Lin. "Establishment of syngeneic murine model for oral cancer therapy." Oral Oncology 95 (August 2019): 194–201. http://dx.doi.org/10.1016/j.oraloncology.2019.06.026.

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Farhoodi, Henry P., Aude I. Segaliny, Zachary W. Wagoner, Jason L. Cheng, Linan Liu, and Weian Zhao. "Optimization of a syngeneic murine model of bone metastasis." Journal of Bone Oncology 23 (August 2020): 100298. http://dx.doi.org/10.1016/j.jbo.2020.100298.

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Mezhir, James J., Kerrington D. Smith, Eric T. Kimchi, James O. Park, Carlos A. Lopez, Helena J. Mauceri, Micheal A. Beckett, Samual Hellman, Ralph R. Weichselbaum, and Mitchell C. Posner. "Establishment of a Syngeneic Model of Hepatic Colorectal Oligometastases." Journal of Surgical Research 136, no. 2 (December 2006): 288–93. http://dx.doi.org/10.1016/j.jss.2006.05.008.

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Mehr, Ramit, Alan S. Perelson, Ayala Sharp, Lee Segel, and Amiela Globerson. "MHC-Linked Syngeneic Developmental Preference in Thymic Lobes Colonized with Bone Marrow Cells: A Mathematical model." Developmental Immunology 5, no. 4 (1998): 303–18. http://dx.doi.org/10.1155/1998/65943.

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Reconstitution of the T-cell compartment after bone marrow transplantation depends on successful colonization of the thymus by bone-marrow-derived progenitor cells. Recent studies compared the development of syngeneic and allogeneic bone-marrow-derived cells in cocultures with lymphoid-depleted fetal thymus explants, leading to the discovery of MHC-linked syngeneic developmental preference (SDP) in the thymus. To determine the nature of cell interactions among the bone marrow and thymic elements that might underlie SDP, we analyzed this phenomenon by mathematical modeling. The results indicate that syngeneic mature T cells, responsible for inducing this preference, probably interfere both with the seeding of allogeneic bone-marrow-derived thymocyte progenitors in the thymic stroma and with their subsequent proliferation. In addition, the possibility of augmented death among the developing allogeneic thymocytes cannot be ruled out.

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Seishima, Noriko, William Becker, Purevdorj Olkhanud, Hoyoung Maeng, Miguel Lopez-Lago, Charles Wiseman, William Williams, and Jay Berzofsky. "Peptide-pulsed MHC class II allogeneic dendritic cell vaccine has superior efficacy providing allogeneic help in a murine cancer model." Journal of Immunology 212, no. 1_Supplement (May 1, 2024): 1097_4946. http://dx.doi.org/10.4049/jimmunol.212.supp.1097.4946.

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Abstract Allogeneic dendritic cell (DC) cancer vaccines present a promising alternative to autologous counterparts, offering an “off-the-shelf” solution for multiple patients and providing additional allogeneic help. We assessed the efficacy of a semi-allogeneic DC vaccine in comparison to a syngeneic one for tumor suppression. C57BL/6 mice were inoculated subcutaneously with human papillomavirus E6 and E7-expressing TC-1 cells. Syngeneic bone marrow DCs (BMDCs) were generated from C57BL/6 and semi-allogeneic BMDCs with a point mutation on either MHC class I or II were generated from B6.C-H2-Kbm1/By and B6(C)-H2-Ab1bm12/KhEg, respectively. The TC-1-bearing mice were injected with syngeneic or semi-allogeneic BMDCs pulsed with H-2Db-restricted E743-77 peptide. Compared with saline control, the MHC-I mutant BMDC vaccine reduced tumor growth no better than the syngeneic one. However, the MHC-II mutant BMDC vaccine was significantly better at delaying tumor growth. CD4+ or CD8+ T cell depletion showed that the syngeneic BMDC vaccine worked independently of CD4+ T cells, but the enhanced activity of the MHC-II mutant BMDC vaccine was dependent on CD4+ T cells at an early stage. Surprisingly, later depletion of CD4+ T cells improved vaccine efficacy, and this was confirmed to be due to Treg depletion. Thus, MHC class II allogeneic BMDCs proved more effective by inducing early allogeneic CD4+ T cell help, and this effect can by further enhanced by Treg depletion at a later stage.

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Ildstad, S. T., J. A. Bluestone, and D. H. Sachs. "Alloresistance to engraftment of allogeneic donor bone marrow is mediated by an Lyt-2+ T cell in mixed allogeneic reconstitution (C57BL/10Sn + B10.D2/nSn----C57BL/10Sn)." Journal of Experimental Medicine 163, no. 5 (May 1, 1986): 1343–48. http://dx.doi.org/10.1084/jem.163.5.1343.

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In the mixed allogeneic reconstitution (B10 + B10.D2----B10) model, alloresistance to engraftment of allogeneic donor results if the syngeneic component of the mixed bone marrow inoculum is not depleted of Lyt-2+ cells before transplantation. Resultant experimental animals repopulate as fully syngeneic, reject B10.D2 skin allografts, and are reactive to B10.D2 lymphoid cells in vitro, as assessed by mixed lymphocyte culture proliferative and cellular cytotoxicity assays. In contrast, depletion of Lyt-2-reactive cells from the syngeneic component of the mixed bone marrow inoculum results in mixed lymphopoietic chimerism and specific in vivo transplantation tolerance to B10.D2 allogeneic donor skin grafts and in vitro unreactivity to B10.D2 lymphoid elements. Full reactivity to third party is evident both in vitro and in vivo in these animals. This model may be helpful in further study of the syngeneic host-type cell phenotypes responsible for alloresistance to bone marrow engraftment.

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Seishima, Noriko, Purevdorj B. Olkhanud, William Becker, Hoyoung Maeng, Miguel Lopez-Lago, Charles Wiseman, William V. Williams, and Jay A. Berzofsky. "Peptide-pulsed MHC class II mutant dendritic cell vaccine has superior efficacy in a murine tumor model." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 159.10. http://dx.doi.org/10.4049/jimmunol.210.supp.159.10.

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Abstract Autologous dendritic cell (DC) vaccines with tumor antigens have been used clinically with limited therapeutic effects. Semi-allogeneic DC-based immunotherapy is still controversial, but it can be an alternative source and more attractive than autologous DC vaccines because the “off-the-shelf” DCs can be used for multiple patients without lengthy individual manufacturing time and may provide additional “allogeneic help”. This study aims to compare efficacy of syngeneic DC vaccines and semi-allogeneic DC vaccines and determine whether a therapeutic semi-allogeneic DC vaccine is more efficacious in tumor suppression. Female C57BL/6 mice were inoculated subcutaneously with human papillomavirus E6 and E7-expressing TC-1 cells. Syngeneic bone marrow dendritic cells (BMDCs) were generated from C57BL/6 and semi-allogeneic BMDCs were generated from two mouse strains, B6.C-H2-K bm1/ByJ and B6(C)-H2-Ab1 bm12/KhEgJ which had limited point mutations in the MHC class I H2-K ballele or H2-lA bMHC class II allele, respectively. Each BMDC was pulsed with H-2D b-restricted E7 43–77peptide and matured before injection. The mice received 4 intradermal injections of syngeneic or one of the semi-allogeneic E7-pulsed BMDC vaccines starting 8–9 days after the TC-1 implantation. Compared with saline control, the MHC class I mutant BMDC vaccine had efficacy similar to the syngeneic BMDC vaccine in suppressing TC-1 tumor growth. However, the MHC class II mutant BMDC vaccine had efficacy significantly superior to that of the other BMDC vaccines. Thus, MHC class II semi-allogeneic BMDCs may be more effective than syngeneic DC-based cancer vaccines, presumably because the class II alloantigens induce additional T cell help for anti-tumor immunity.

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Chade, Daher C., Priscila M. Andrade, Ricardo C. Borra, Katia R. Leite, Enrico Andrade, Fabiola E. Villanova, and Miguel Srougi. "Histopathological characterization of a syngeneic orthotopic murine bladder cancer model." International braz j urol 34, no. 2 (March 2008): 220–29. http://dx.doi.org/10.1590/s1677-55382008000200013.

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Quinn, Bridget A., Fang Xiao, Laura Bickel, Lainie Martin, Xiang Hua, Andres Klein-Szanto, and Denise C. Connolly. "Development of a syngeneic mouse model of epithelial ovarian cancer." Journal of Ovarian Research 3, no. 1 (2010): 24. http://dx.doi.org/10.1186/1757-2215-3-24.

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Steel, Jason C., Brian J. Morrison, Poonam Mannan, Gregory A. Prince, Kevin C. Yim, Brian K. Miles, Oliver Wildner, and John C. Morris. "322. Syngeneic Cotton Rat Cancer Model for Replicating Adenoviral Vectors." Molecular Therapy 13 (2006): S123. http://dx.doi.org/10.1016/j.ymthe.2006.08.379.

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Chan, Eddie S. Y., Amit R. Patel, Armine K. Smith, John B. Klein, Anil A. Thomas, Warren D. Heston, and William A. Larchian. "Optimizing Orthotopic Bladder Tumor Implantation in a Syngeneic Mouse Model." Journal of Urology 182, no. 6 (December 2009): 2926–31. http://dx.doi.org/10.1016/j.juro.2009.08.020.

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Pénzváltó, Zsófia, Jane Qian Chen, Clifford G. Tepper, Ryan R. Davis, Matthew T. Silvestrini, Maxine Umeh-Garcia, Colleen Sweeney, and Alexander D. Borowsky. "A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials." Journal of Mammary Gland Biology and Neoplasia 24, no. 2 (February 27, 2019): 149–62. http://dx.doi.org/10.1007/s10911-019-09425-3.

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Brady, A., E. Pedraza, A. Pileggi, C. Ricordi, and C. Stabler. "MACROPOROUS BIOENGINEERED SCAFFOLDS FOR ISLET TRANSPLANTATION - A SYNGENEIC MOUSE MODEL." Transplantation Journal 90 (July 2010): 1007. http://dx.doi.org/10.1097/00007890-201007272-01974.

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Weiner, Ned E., Richard B. Pyles, Claudia L. Chalk, M. Gregory Balko, Mary Ann Miller, Charissa A. Dyer, Ronald E. Warnick, and Linda M. Parysek. "A Syngeneic Mouse Glioma Model for Study of Glioblastoma Therapy." Journal of Neuropathology and Experimental Neurology 58, no. 1 (January 1999): 54–60. http://dx.doi.org/10.1097/00005072-199901000-00007.

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Semilietof, Aikaterini, Evangelos Stefanidis, Elise Gray-Gaillard, Julien Pujol, Alessia D'Esposito, Patrick Reichenbach, Philippe Guillaume, Vincent Zoete, Melita Irving, and Olivier Michielin. "Preclinical model for evaluating human TCRs against chimeric syngeneic tumors." Journal for ImmunoTherapy of Cancer 12, no. 12 (December 2024): e009504. https://doi.org/10.1136/jitc-2024-009504.

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BackgroundThe adoptive cell transfer (ACT) of T cell receptor (TCR)-engineered T cells targeting the HLA-A2-restricted epitope NY-ESO-1157-165(A2/NY) has yielded important clinical responses against several cancers. A variety of approaches are being taken to augment tumor control by ACT including TCR affinity-optimization and T-cell coengineering strategies to address the suppressive tumor microenvironment (TME). Most TCRs of clinical interest are evaluated in immunocompromised mice to enable human T-cell engraftment and do not recapitulate the dynamic interplay that occurs with endogenous immunity in a treated patient. A variety of humanized mouse models have been described but they have limitations in immune reconstitution and are technically challenging to implement. Here, we have developed a chimeric syngeneic tumor model in which A2Kb transgenic C57BL/6 mice are engrafted with B16 expressing A2Kb:NY as a single chain trimer (SCT) and treated by ACT with murine T cells expressing A2/NY TCRs comprising human variable fused to mouse constant regions.MethodsWe compared the function of a supraphysiological affinity A2/NY TCR (wtc51m), a computationally designed TCR in an optimal affinity range (DMβ), and a near non-binding TCR (V49I), engineered in both primary human and murine T cells by lentiviral and retroviral transduction, respectively. We evaluated a variety of strategies to stably express A2Kb:NY on the surface of mouse tumor cell lines including B16 melanoma, ultimately achieving success with an SCT comprising human β2m fused by GS linkers to both the NY-peptide and to α1 of the HLA complex. ACT studies were performed in B16-A2Kb:NY tumor-bearing, non-preconditioned immune-competent HLA-A*0201/H-2Kb (A2Kb) transgenic C57BL/6 mice and tumors characterized post-transfer.ResultsWe observed significantly improved function of DMβ-T cells as well as superior infiltration and tumor control upon ACT as compared to the control TCR-T cells. Moreover, with our chimeric syngeneic tumor model, we were able to track dynamic and favorable changes in the TME upon DMβ-T cell transfer.ConclusionsWe have developed a robust, simple, and inexpensive preclinical strategy for evaluating human TCRs in the context of a fully competent murine immune system that can aid in the development of coengineered TCR-T cells and combination treatments translated to the clinic.

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Moon, Hyeong-Gon, Hye Youn Son, Woo Hang Heo, Mingji Quan, SONGBIN LI, Haritonova Valentina, Hamin Jeong, et al. "Abstract P2-20-05: Personalized tumor vaccine can suppress tumor growth and metastasis in the syngeneic mouse breast cancer model." Cancer Research 83, no. 5_Supplement (March 1, 2023): P2–20–05—P2–20–05. http://dx.doi.org/10.1158/1538-7445.sabcs22-p2-20-05.

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Abstract Objective Immunotherapy using the tumor-specific antigens (TSAs) is a promising strategy in breast cancer. Studies have suggested that the in vivo exposures to certain tumors can induce adaptive anti-tumor immunity in syngeneic tumor models. In this study, we show the efficacy of the tumor lysate vaccine and peptide-based vaccine against tumor neoantigen in suppressing tumor growth and metastasis in 4T1 syngeneic tumor models. Method We used BALB/c mice and its syngeneic tumor cell lines to evaluate the anti-tumor effect induced by the transient exposure to the tumor cells. For tumor vaccines, we synthesized the tumor lysate vaccine by the freeze-thaw method or synthetic peptide against the selected tumor neoantigens identified by exome sequencing. We systemic and local immune remodeling was investigated by using immunohistochemistry, flow cytometry, and single cell RNA sequencing. Results We observed a significant reduction of tumor growth and metastasis in 4T1 syngeneic tumors when the mice were previously exposed to the same cells (pre-exposure group). This anti-tumor effect induced by the exposures to the tumor was cell line-specific. The 4T1 tumor lysate vaccines administered prior to the tumor cell injection also showed significant inhibitory effect on tumor growth and metastasis. T lymphocytes, isolated from the tumor tissues of the 4T1 pre-exposure mice and lysate vaccine-treated mice, showed higher levels of TNF-ɑ and IFN-ɣ when compared to the control those from the control tumors. The lysate vaccine treatment resulted in a substantial remodeling of tumor microenvironment including reduction of myeloid-derived suppressor cells and M2 tumor-associated macrophages. On the other hand, the numbers of M1 tumor-associated macrophages and effector memory CD8+ T cells were increased by the lysate vaccine. While the peptide vaccine showed no inhibitory effect on the primary tumor growth, it also suppressed spontaneous lung metastasis. Finally, we administered lysate tumor vaccine after the tumor establishment to determine the therapeutic effect. The lysate vaccine significantly suppressed the tumor growth and lung metastasis of the syngeneic 4T1 tumors. Conclusion Tumor lysate vaccine can suppress the tumor growth and metastasis in the 4T1 syngeneic mouse models by inducing substantial remodeling of tumor immune microenvironment. Additionally, tumor lysate vaccine can elicit similar anti-tumor immune response when administered after the establishment of the primary tumor suggesting a potential therapeutic value. Citation Format: Hyeong-Gon Moon, Hye Youn Son, Woo Hang Heo, Mingji Quan, SONGBIN LI, Haritonova Valentina, Hamin Jeong, Wonshik Han, Han-Byoel Lee, YUJEONG HER, Ju Hee Kim. Personalized tumor vaccine can suppress tumor growth and metastasis in the syngeneic mouse breast cancer model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-20-05.

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Chamo, Michael, Omri Koren, Oron Goldstein, Nir Bujanover, Nurit Keinan, Ye’ela Scharff, and Roi Gazit. "Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells." Cancers 15, no. 3 (January 24, 2023): 720. http://dx.doi.org/10.3390/cancers15030720.

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Acute Myeloid Leukemia (AML) is a severe disease with a very high relapse rate. AML relapse may be attributable to leukemic stem cells (LSC). Notably, the “cancer stem cell” theory, which relates to LSCs, is controversial and criticized due to the technical peculiarities of the xenotransplant of human cells into mice. In this study, we searched for possible LSCs in an immunocompetent synergetic mice model. First, we found phenotypic heterogeneity in the ML23 leukemia line. We prospectively isolated a sub-population using the surface markers cKit+CD9-CD48+Mac1-/low, which have the potency to relapse the disease. Importantly, this sub-population can pass in syngeneic hosts and retrieve the heterogeneity of the parental ML23 leukemia line. The LSC sub-population resides in various organs. We present a unique gene expression signature of the LSC in the ML23 model compared to the other sub-populations. Interestingly, the ML23 LSC sub-population expresses therapeutic targeted genes such as CD47 and CD93. Taken together, we present the identification and molecular characterization of LSCs in a syngeneic murine model.

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Zhang, Wenlong, Xiangyu Chen, Dong Ding, Guoxin Zhang, Ziwei Zhu, XingJiu Yang, Mengyuan Li, et al. "Real-time in vivo imaging reveals specific nanoparticle target binding in a syngeneic glioma mouse model." Nanoscale 14, no. 15 (2022): 5678–88. http://dx.doi.org/10.1039/d1nr07591h.

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Joachim, Anais, Emilie Maturin, Marielle Mello, Lilia Hadjem, Magali Grange, Olivier Deas, Ana Zarubica, et al. "Abstract 86: Deep immuno-profiling of syngeneic tumor mouse models for preclinical studies." Cancer Research 84, no. 6_Supplement (March 22, 2024): 86. http://dx.doi.org/10.1158/1538-7445.am2024-86.

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Abstract The identification of the major cellular players involved in the progression of a type of cancer is a key step for the success of new immunotherapies for personalized medicine. Immune cells play critical functions in cancer, and mice with intact immune systems are vital to understanding tumor immunology. It is however a daunting challenge as complex relationships interplay between tumor cells and the immune system. Each component of innate immunity or adaptive immunity, such as T lymphocytes, macrophages or neutrophils, may be directed to a pro- or anti-tumor function. In order to cope with the complexity of the tumor microenvironment, it is necessary to use an experimental approach capable of characterizing the heterogeneity of the cell types present in the tumor, the evolution of their relative proportion and their fine-tuned functional specificity. This approach leads to the identification of new cellular biomarkers of different stages of tumor progression in order to identify new targets for therapeutic time-window of and improve cancer diagnosis To decipher the impact of immunotherapy treatments involved in the anti-tumor response, cellular phenotyping of leukocytes infiltrating a tumor but also those present in peripheral organs is necessary. Essentially based on extracellular labeling, this primary screen aims to quantify the different cell populations present in a syngenic tumor models on B6/N or BalbC genetical backgrounds. In order to increase our understanding in the precise mode of action of anti-PD1 treatment at the cellular level in sensitive and unsensitive models, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) of several hallmark syngeneic tumor models (MC38, CT26, B16F10, B16-OVA, RENCA, EMT6) in immunocompetent mouse models by flow and mass cytometry. We compared growth kinetics and profiled the immune cell composition of tumor microenvironment (TME), draining lymph node (dLN) and blood in order to establish immune-phenotypic cell signatures that correlates with treatment efficacy. Supervised, unsupervised and integrative data analysis as well as visualization tools are used to identify significant changes across different experimental settings. Our results indicate that each model possesses a unique tumor-immune infiltrate profile that can be modulated with immunotherapies. Overall, these studies provide an important resource of highly-characterized syngeneic tumor model and highlight the importance of tumor immune landscape variance across models that will drive selecting the most appropriate model to test novel immunotherapeutic agents and enhance our translation of knowledge from syngeneic models to human tumors. Citation Format: Anais Joachim, Emilie Maturin, Marielle Mello, Lilia Hadjem, Magali Grange, Olivier Deas, Ana Zarubica, Bernard Malissen, Hervé Luche, François Romagne, Stéphanie Blanchin. Deep immuno-profiling of syngeneic tumor mouse models for preclinical studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 86.

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Stathopoulos, Apostolos, G. Milbouw, and T. Chen. "Elimination of Intracranial Gliomas via Immune Rejection of Subcutaneous Allogeneic Glioma Cell Lysate (48.40)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): S82. http://dx.doi.org/10.4049/jimmunol.178.supp.48.40.

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Abstract Allogeneic glioma cell lines, coupled with allogeneic and syngeneic tumor cell lysates, could be used to induce immune mediated rejection of syngeneic glioma cell lines in two strains of rat. Fisher344 and Sprague Dawley (SD) rats were implanted subcutaneously with 9L and C6 glioma cell lines. After tumor formation, rats were injected subcutaneously with a combination of allogeneic tumor cell line and combined allogeneic and syngeneic tumor lysate. As a further study, treated rats, who had decreased tumor size from the above treatment, were tested for immune memory. Same experiments were also performed in the intracranial model. Rats treated with the same methode were able to significantly reduce (Fisher344), or completely reject (SD rats), their tumor. “Cured” rats re-injected with five times the original number of malignant cells and remained tumor free. Analysis of these tumors shows numbers of CD4, CD8, B-lymphocytes, and dendritic cells. In the intracranial model, rats had significantly less intracranial spread of tumor than the control group. Our in vivo experiments demonstrate that established subcutaneous or intracranial gliomas may be treated with a combination of allogeneic cells and tumor lysates (allogeneic and syngeneic tumor cells) to reduce its size or eliminate it, and establish lasting memory.

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Park, Seung Bum, Wansang Cho, Won Sol Chan, young il choi, Sungoh Ahn, and Dong-Sup Lee. "Abstract 667: Inhibition of protein-protein interaction between STING and TRIM29 is a new approach to enhance anti-tumor immune response." Cancer Research 82, no. 12_Supplement (June 15, 2022): 667. http://dx.doi.org/10.1158/1538-7445.am2022-667.

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Abstract Introduction: STimulator of INterferon Genes (STING) has been reported to be essential for antitumor immunity by inducing type I IFN expression, resulting in activation of both innate and adaptive immunity. Thus, pharmacological activation of STING pathway is actively being tested in many clinical studies. However, the clinical efficacy was not that clear, probably due to the limited expression of STING protein, which is tightly regulated by TRIM29 (E3 ligase)-mediated protein degradation pathway. Here, we present a novel small-molecule drug candidate with strong antitumor response in murine syngeneic model by upregulating cellular levels of STING through the inhibition of protein-protein interaction. Methods: The inhibitors of STING-TRIM29 interaction were identified using luciferase-complementation high-throughput screening system. Target protein of the inhibitor was identified in cellular thermostability shift assay. Their immunological activity was tested in Raw264.7 and A431 cells as well as CT26 murine syngeneic model. Results: The lead compound, SB24011, bound to STING and upregulated cellular levels of STING by inhibiting ubiquitin-mediated degradation. Together with STING agonist, SB24011 synergistically enhanced the inflammatory cytokine expression in cell lines as well as in CT26 syngeneic animal model. Intratumoral injection of SB24011 showed strong abscopal activity as single agent as well as synergistic antitumor responses with anti-PD1 antibody in CT26 syngeneic animal model. Conclusions: We identified novel small-molecule drug candidate, SB24011, which prevents the degradation of both murine and human STING proteins, resulting in enhanced immune responses together with STING agonist, cGAMP. SB24011 showed strong abscopal antitumor activity as single agent and synergistic antitumor activity as combination agent with other IO agents in CT26 syngeneic models. Citation Format: Seung Bum Park, Wansang Cho, Won Sol Chan, young il choi, Sungoh Ahn, Dong-Sup Lee. Inhibition of protein-protein interaction between STING and TRIM29 is a new approach to enhance anti-tumor immune response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 667.

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Ghosh, Sanjana, Xuedan He, Wei-Chiao Huang, and Jonathan F. Lovell. "Immune checkpoint blockade enhances chemophototherapy in a syngeneic pancreatic tumor model." APL Bioengineering 6, no. 3 (September 1, 2022): 036105. http://dx.doi.org/10.1063/5.0099811.

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Pancreatic cancer (PaCa) suffers from poor treatment options for locally advanced cases. Chemophototherapy (CPT) is an emerging anti-tumor modality, and porphyrin–phospholipid liposomes have been shown to be versatile drug carriers for CPT in preclinical rodent models. Here we show that in the syngeneic subcutaneous KPC PaCa tumor model, exhausted CD8+ T cells are localized in the tumor, and that CPT is enhanced in combination with immune checkpoint blockade (ICB). Addition of ICB using anti-programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies resulted in ablation of medium-sized, established KPC tumors (∼200 mm3) without recurrence for over 100 days. Mice rejected subsequent tumor re-challenge. Flow cytometry and tumor slice analysis following injection of a fluorescently labeled anti-PD-1 antibody showed that CPT improved antibody delivery to the tumor microenvironment. Treatment of large established tumors (∼400 mm3) using with CPT and ICB induced appreciable tumor regression and delay in regrowth. Taken together, these data demonstrate the utility of combining CPT with immunotherapies.

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Haughey, Charles M., Debayan Mukherjee, Rebecca E. Steele, Amy Popple, Lara Dura-Perez, Adam Pickard, Mehjabin Patel, et al. "Investigating Radiotherapy Response in a Novel Syngeneic Model of Prostate Cancer." Cancers 12, no. 10 (September 29, 2020): 2804. http://dx.doi.org/10.3390/cancers12102804.

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The prostate cancer (PCa) field lacks clinically relevant, syngeneic mouse models which retain the tumour microenvironment observed in PCa patients. This study establishes a cell line from prostate tumour tissue derived from the Pten−/−/trp53−/− mouse, termed DVL3 which when subcutaneously implanted in immunocompetent C57BL/6 mice, forms tumours with distinct glandular morphology, strong cytokeratin 8 and androgen receptor expression, recapitulating high-risk localised human PCa. Compared to the commonly used TRAMP C1 model, generated with SV40 large T-antigen, DVL3 tumours are immunologically cold, with a lower proportion of CD8+ T-cells, and high proportion of immunosuppressive myeloid derived suppressor cells (MDSCs), thus resembling high-risk PCa. Furthermore, DVL3 tumours are responsive to fractionated RT, a standard treatment for localised and metastatic PCa, compared to the TRAMP C1 model. RNA-sequencing of irradiated DVL3 tumours identified upregulation of type-1 interferon and STING pathways, as well as transcripts associated with MDSCs. Upregulation of STING expression in tumour epithelium and the recruitment of MDSCs following irradiation was confirmed by immunohistochemistry. The DVL3 syngeneic model represents substantial progress in preclinical PCa modelling, displaying pathological, micro-environmental and treatment responses observed in molecular high-risk disease. Our study supports using this model for development and validation of treatments targeting PCa, especially novel immune therapeutic agents.

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Ellis, Leigh, Kristin Lehet, ShengYu Ku, Gissou Azabdaftari, and Roberto Pili. "Generation of a syngeneic orthotopic transplant model of prostate cancer metastasis." Oncoscience 1, no. 10 (October 15, 2014): 609–13. http://dx.doi.org/10.18632/oncoscience.88.

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Zhang, Xu Dong, Grant David Schiller, Peter Grantly Gill, and Brendon John Coventry. "Lymphoid cell infiltration during breast cancer growth: A syngeneic rat model." Immunology and Cell Biology 76, no. 6 (December 1998): 550–55. http://dx.doi.org/10.1046/j.1440-1711.1998.00780.x.

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Wilkinson-Ryan, Ivy, Melissa M. Pham, Petra Sergent, Laura J. Tafe, and Brent L. Berwin. "A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases." Translational Oncology 12, no. 1 (January 2019): 62–68. http://dx.doi.org/10.1016/j.tranon.2018.08.020.

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Hewitt, A. "Soy extract inhibits mammary adenocarcinoma growth in a syngeneic mouse model." Cancer Letters 192, no. 2 (March 31, 2003): 133–43. http://dx.doi.org/10.1016/s0304-3835(02)00712-7.

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White-Gilbertson, Shai, Megan Davis, Christina Voelkel-Johnson, and Laura M. Kasman. "Sex differences in the MB49 syngeneic, murine model of bladder cancer." Bladder 3, no. 1 (February 24, 2016): 22. http://dx.doi.org/10.14440/bladder.2016.73.

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Mathieu, David, Roger Lecomte, Ana Maria Tsanaclis, Annie Larouche, and David Fortin. "Standardization and Detailed Characterization of the Syngeneic Fischer/F98 Glioma Model." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 34, no. 3 (August 2007): 296–306. http://dx.doi.org/10.1017/s0317167100006715.

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Introduction:Adequate animal glioma models are mandatory for the pursuit of preclinical research in neuro-oncology. Many implantation models have been described, but none perfectly emulate human malignant gliomas. This work reports our experience in standardizing, optimizing and characterizing the Fischer/F98 glioma model on the clinical, pathological, radiological and metabolic aspects.Materials and methods:F98 cells were implanted in 70 Fischer rats, varying the quantity of cells and volume of implantation solution, and using a micro-infusion pump to minimize implantation trauma, after adequate coordinates were established. Pathological analysis consisted in hematoxylin and eosin (H&E) staining and immunohistochemistry for GFAP, vimentin, albumin, TGF-b1, TGF-b2, CD3 and CD45. Twelve animals were used for MR imaging at 5, 10, 15 and 20 days. Corresponding MR images were compared with pathological slides. Two animals underwent 18F-FDG and 11C-acetate PET studies for metabolic characterization of the tumors.Results:Implantation with 1x104 cells produced a median survival of 26 days and a tumor take of 100%. Large infiltrative neoplasms with a necrotic core were seen on H&E. Numerous mitosis, peritumoral infiltrative behavior, and neovascular proliferation were also obvious. GFAP and vimentin staining was positive inside the tumor cells. Albumin staining was observed in the extracellular space around the tumors. CD3 staining was negligible. The MR images correlated the pathologic findings. 18F-FDG uptake was strong in the tumors.Conclusion:The standardized model described in this study behaves in a predictable and reproducible fashion, and could be considered for future pre-clinical studies. It adequately mimics the behavior of human malignant astrocytomas.

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Rashid, Omar M., Masayuki Nagahashi, Suburamaniam Ramachandran, Catherine Dumur, Julia Schaum, Akimitsu Yamada, Krista P. Terracina, Sheldon Milstien, Sarah Spiegel, and Kazuaki Takabe. "An improved syngeneic orthotopic murine model of human breast cancer progression." Breast Cancer Research and Treatment 147, no. 3 (September 9, 2014): 501–12. http://dx.doi.org/10.1007/s10549-014-3118-0.

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Goldsberry, W., J. A. Wall, S. Meza-Perez, A. A. Katre, A. I. Londono, L. A. Norian, T. Randall, and R. C. Arend. "Inhibition of PORCN in a p53-/- knockout syngeneic ovarian cancer model." Gynecologic Oncology 159 (October 2020): 93. http://dx.doi.org/10.1016/j.ygyno.2020.05.079.

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Federico, Lorenzo, Zechen Chong, Dong Zhang, Daniel J. McGrail, Wei Zhao, Kang Jin Jeong, Christopher P. Vellano, et al. "A murine preclinical syngeneic transplantation model for breast cancer precision medicine." Science Advances 3, no. 4 (April 2017): e1600957. http://dx.doi.org/10.1126/sciadv.1600957.

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Uonaga, Taeko, Kentaro Toyoda, Teru Okitsu, Xiaotong Zhuang, Shunsuke Yamane, Shinji Uemoto, and Nobuya Inagaki. "FGF-21 enhances islet engraftment in mouse syngeneic islet transplantation model." Islets 2, no. 4 (July 2010): 247–51. http://dx.doi.org/10.4161/isl.2.4.12402.

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Williams, Sharon A., Yuka Harata-Lee, Iain Comerford, Robin L. Anderson, Mark J. Smyth, and Shaun R. McColl. "Multiple functions of CXCL12 in a syngeneic model of breast cancer." Molecular Cancer 9, no. 1 (2010): 250. http://dx.doi.org/10.1186/1476-4598-9-250.

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Slastnikova, Tatiana A., Andrey A. Rosenkranz, Alexey V. Ulasov, Yuri V. Khramtsov, Tatiana N. Lupanova, Georgii P. Georgiev, and Alexander S. Sobolev. "Mouse Syngeneic Melanoma Model with Human Epidermal Growth Factor Receptor Expression." Pharmaceutics 14, no. 11 (November 12, 2022): 2448. http://dx.doi.org/10.3390/pharmaceutics14112448.

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The development of epidermal growth factor receptor (EGFR)-targeting agents for the treatment of malignant melanoma requires cheap and easy animal tumor models for high-throughput in vivo screening. Thus, the aim of this study was to develop mouse syngeneic melanoma model that expresses human EGFR. Cloudman S91 clone M3 mouse melanoma cells were transduced with lentiviral particles carrying the human EGFR gene followed by a multistep selection process. The resulting M3-EGFR has been tested for EGFR expression and functionality in vitro and in vivo. Radioligand assay confirmed the presence of 13,900 ± 1500 EGF binding sites per cell at a dissociation constant of 5.3 ± 1.4 nM. M3-EGFR demonstrated the ability to bind and internalize specifically and provide the anticipated intracellular nuclear import of three different EGFR-targeted modular nanotransporters designed for specific anti-cancer drug delivery. Introduction of the human EGFR gene did not alter the tumorigenicity of the offspring M3-EGFR cells in host immunocompetent DBA/2J mice. Preservation of the expression of EGFR in vivo was confirmed by immunohistochemistry. To sum up, we successfully developed the first mouse syngeneic melanoma model with preserved in vivo expression of human EGFR.

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Leung, Brendan M., Yasuo Miyagi, Ren-Ke Li, and Michael V. Sefton. "Fate of modular cardiac tissue constructs in a syngeneic rat model." Journal of Tissue Engineering and Regenerative Medicine 9, no. 11 (March 15, 2013): 1247–58. http://dx.doi.org/10.1002/term.1724.

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Taus, Luke J., Roberto E. Flores, and Thomas N. Seyfried. "Quantification of metastatic load in a syngeneic murine model of metastasis." Cancer Letters 405 (October 2017): 56–62. http://dx.doi.org/10.1016/j.canlet.2017.07.011.

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Yu, Yi, Yang Zhao, Guangming Zhou, and Xiang Wang. "Therapeutic Efficacy of Delta-Like Ligand 4 Gene Vaccine Overexpression on Liver Cancer in Mice." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382094220. http://dx.doi.org/10.1177/1533033820942205.

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Delta-like ligand 4 is a notch ligand that is predominantly expressed in the endothelial tip cells and plays essential roles in the regulation of angiogenesis. In this study, we explored the therapeutic effects of delta-like ligand 4 gene vaccine overexpression on the syngeneic model mouse model of liver cancer and the underlying mechanisms. Mouse hepatocellular carcinoma cell line H22-H8D8 was used to generate subcutaneous syngeneic model liver cancer in Kunming mice, and the effects of recombinant plasmid pVAX1 containing delta-like ligand 4 vaccine on tumor growth was examined. Compared to controls, delta-like ligand 4 vaccination reduced syngeneic model tumor size by 70.31% (from 17.11 ± 9.30 cm3 to 5.08 ± 2.75 cm3, P = .035) and tumor weight by 34.19% (from 6.26 ± 3.01 g to 4.12 ± 2.52 g, P = .102), while the mouse survival was significantly increased (from 27.7 ± 6.0 days to 33.1 ± 6.1 days, P = .047). High level of delta-like ligand 4 antibody, together with a significantly increased number of CD4+ and decreased CD8+ cells were identified in the mouse peripheral blood serum samples after delta-like ligand 4 immunization. In addition, elevated serum levels of interleukin 2, interleukin 4, and interferon γ were detected in the delta-like ligand 4–vaccinated mice when compared to the controls. Further studies have revealed increased CD31 and decreased Ki67 expression in the syngeneic model tumor tissues of vaccinated mice. Taken together, our studies suggest that delta-like ligand 4 gene vaccine can inhibit the growth of hepatocellular carcinoma in mice through inhibiting tumor angiogenesis and boosting antitumor immune responses. Hence, delta-like ligand 4 gene vaccination may be a promising strategy for the treatment of transplanted liver cancer.

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Jantscheff, Peter, Janette Beshay, Thomas Lemarchand, Cynthia Obodozie, Christoph Schächtele, and Holger Weber. "Mouse-Derived Isograft (MDI) In Vivo Tumor Models I. Spontaneous sMDI Models: Characterization and Cancer Therapeutic Approaches." Cancers 11, no. 2 (February 19, 2019): 244. http://dx.doi.org/10.3390/cancers11020244.

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Syngeneic in vivo tumor models are valuable for the development and investigation of immune-modulating anti-cancer drugs. In the present study, we established a novel syngeneic in vivo model type named mouse-derived isografts (MDIs). Spontaneous MDIs (sMDIs) were obtained during a long-term observation period (more than one to two years) of naïve and untreated animals of various mouse strains (C3H/HeJ, CBA/J, DBA/2N, BALB/c, and C57BL/6N). Primary tumors or suspicious tissues were assessed macroscopically and re-transplanted in a PDX-like manner as small tumor pieces into sex-matched syngeneic animals. Nine outgrowing primary tumors were histologically characterized either as adenocarcinomas, histiocytic carcinomas, or lymphomas. Growth of the tumor pieces after re-transplantation displayed model heterogeneity. The adenocarcinoma sMDI model JA-0009 was further characterized by flow cytometry, RNA-sequencing, and efficacy studies. M2 macrophages were found to be the main tumor infiltrating leukocyte population, whereas only a few T cells were observed. JA-0009 showed limited sensitivity when treated with antibodies against inhibitory checkpoint molecules (anti-mPD-1 and anti-mCTLA-4), but high sensitivity to gemcitabine treatment. The generated sMDI are spontaneously occurring tumors of low passage number, propagated as tissue pieces in mice without any tissue culturing, and thus conserving the original tumor characteristics and intratumoral immune cell populations.

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Shin, Sung-Won, Kyungmi Yang, Miso Lee, Jiyoung Moon, Arang Son, Yeeun Kim, Suha Choi, et al. "Manganese Ferrite Nanoparticles Enhance the Sensitivity of Hepa1-6 Hepatocellular Carcinoma to Radiation by Remodeling Tumor Microenvironments." International Journal of Molecular Sciences 22, no. 5 (March 5, 2021): 2637. http://dx.doi.org/10.3390/ijms22052637.

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We evaluated the effect of manganese ferrite nanoparticles (MFN) on radiosensitization and immunologic responses using the murine hepatoma cell line Hepa1-6 and the syngeneic mouse model. The clonogenic survival of Hepa1-6 cells was increased by hypoxia, while being restricted by ionizing radiation (IR) and/or MFN. Although MFN suppressed HIF-1α under hypoxia, the combination of IR and MFN enhanced apoptosis and DNA damage in Hepa1-6 cells. In the Hepa1-6 syngeneic mouse model, the combination of IR and MFN notably limited the tumor growth compared to the single treatment with IR or MFN, and also triggered more frequent apoptosis in tumor tissues than that observed under other conditions. Increased expression of PD-L1 after IR was not observed with MFN alone or the combination of IR and MFN in vitro and in vivo, and the percentage of tumor-infiltrating T cells and cytotoxic T cells increased with MFN, regardless of IR, in the Hepa1-6 syngeneic mouse model, while IR alone led to T cell depletion. MFN might have the potential to overcome radioresistance by alleviating hypoxia and strengthening antitumor immunity in the tumor microenvironment.

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Wang, Jessie, Kaixia Lian, Jia Zheng, Chenpan Nie, Annie An, and Henry Li. "323 Immunogenic syngeneic model MC38-OVA for the preclinical evaluation of immune evasion and checkpoint blockade." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A348. http://dx.doi.org/10.1136/jitc-2021-sitc2021.323.

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BackgroundThe development of immuno-oncology (I/O) therapeutics has revolutionized the cancer treatment landscape. Despite this achievement, the mechanism behind limited responses is poorly understood. Tumor immune evasion has been reported to arise through the loss of tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways, which are crucial to CD8+ T cell-mediated killing. Syngeneic mouse models have been widely used as they have an intact immune system, are easily accessible, and have a vast array of historical data for comparison. However, limited syngeneic models respond to immune checkpoint inhibitors, possibly due to low intrinsic immunogenicity. The expression of ovalbumin (OVA) has previously shown to sufficiently alter the susceptibility of syngeneic tumors to host T cell-mediated responses. In this study, the newly developed OVA-expressing MC38 syngeneic line was characterized for tumor immunity, checkpoint blockade response and response durability.MethodsMurine colon cancer MC38 cells were transduced by lentiviral vector with chicken OVA coding cDNA. A single clone was selected, and OVA expression was confirmed by western blot. The MC38-OVA cells were subcutaneously implanted into immunocompetent mice to evaluate the tumorigenicity and in vivo response to anti-PD-1 antibody treatment. Blood was collected 2 days post final dose of anti-PD-1 treatment for phenotypic analysis by FACS. Spleen and tumor draining lymph nodes were collected at termination for FACS analysis of IFN-γ+ T cells and OVA specific CD8+ T cells. Adoptive transfer was evaluated by challenge studies in both MC38-OVA and MC38 tumor-bearing mice with T cells derived from MC38-OVA mice, anti-PD-1 cured mice and OT-I mice. In vitro killing assays were performed to evaluate the function of adoptive CD3+ T cells transfer.ResultsOVA-expressing MC38 presented complete regression under anti-PD-1 treatment in vivo. T cell expansion was observed after anti-PD-1 treatment in peripheral blood with increased IFN-γ+ T cells in both tumor-draining lymph nodes and spleen. Additionally, anti-PD-1 cured mice generated robust tumor specific memory T cell, which successfully inhibited MC38-OVA and MC38 tumor growth following adoptive transfer. CD3+ T cells from MC38-OVA-bearing mice and OT-I mice showed anti-tumor immunity in vivo. In vitro killing assay demonstrated increased immunity.ConclusionsSyngeneic mouse tumor models are preferred preclinical models for I/O research, despite limited intrinsic immunogenicity. OVA expression in syngeneic tumors largely increased T cell-mediated immunity to enhance antigen-specific T cell responses during tumorigenesis, providing novel immunogenic models for preclinical immunotherapy evaluation.

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Sutton, R., D. W. Gray, P. McShane, M. J. Dallman, and P. J. Morris. "The specificity of rejection and the absence of susceptibility of pancreatic islet beta cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat." Journal of Experimental Medicine 170, no. 3 (September 1, 1989): 751–62. http://dx.doi.org/10.1084/jem.170.3.751.

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The specificity of rejection of isolated pancreatic islets was examined in the rat using a quantitative model in which syngeneic (DA) or a mixture of syngeneic and allogeneic (DA and LEW or PVG) islets were implanted beneath the capsule of the kidney of nondiabetic normal rats (DA). 3 wk after transplantation total insulin extraction assays of the kidney with its islet implant together with immunohistological examination of the site of transplantation for evidence of syngeneic or allogeneic tissue demonstrated the total destruction of allogeneic islets without any evidence of damage to syngeneic islets either distant or in immediate proximity to allogeneic islets. Pancreatic islets, and especially beta cells, appear to be particularly vulnerable to the effector arm of both autoimmune and alloimmune responses, a vulnerability that has been attributed to the cytotoxic effects of lymphokines, notably IL-1, released in both autoimmune and alloimmune responses. The experiments reported here demonstrate not only the exquisite specificity of the allograft reaction but are not compatible with a hypothesis that B cells within an intact islet are nonspecifically susceptible to destruction by lymphokines.

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Gunn, Lacey, Yihua Cai, Chuanlin Ding, Xiaoling Hu, Richard Hansen, Deep Aggarwal, and Jun Yan. "Role of complement activation component C5a on tumor progression (100.9)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 100.9. http://dx.doi.org/10.4049/jimmunol.184.supp.100.9.

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Abstract Enhancement of anti-tumor mAb immunological mechanisms for tumor destruction may be obtained by promoting complement activation. However, complement activation components, such as C5a, trigger inflammation and chronic inflammation promotes tumor growth. Recently, it has been shown that C5a in the tumor could recruit and activate myeloid-derived suppressor cells to inhibit the anti-tumor CD8 T cell response. However, this effect was observed in only one tumor model. We chose to address the role of C5a on tumor growth by transfecting tumor cells with C5a. A human ovarian carcinoma, SKOV-3, and a murine lymphoma, RMA, were transfected which allows us to study C5a in an immunocompromised xenograft model and an immunocompetent syngeneic model. In vitro growth kinetics observed revealed no significant difference between C5a, control vector (CV), or wild-type cells. In both models, tumor-bearing mice with C5a-transfected tumor cells have significantly less tumor burden as compared to CV tumors. In the xenograft model, CD11b+DX5+ NK cells were significantly more and VEGF and arginase levels were significantly less in C5a expressing tumors. The syngeneic lymphoma model revealed C5a modulates tumor-infiltrating CD11b+ cells to produce more IL-12 and there is a greater influx of NK and CD4 T cells. Thus our studies demonstrate C5a chemoattracts innate NK cells and downregulates negative mediators in the xenograft model while in the syngeneic model C5a promotes shift to a Th1 response.

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De Ruysscher, D., H. Sobis, M. Vandeputte, and M. Waer. "A subset of asialo GM1+ cells play a protective role in the occurrence of graft-versus-host disease in mice." Journal of Immunology 146, no. 12 (June 15, 1991): 4065–70. http://dx.doi.org/10.4049/jimmunol.146.12.4065.

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Abstract In three different murine models of bone marrow (BM) transplantation the capacity of asialo GM1+ cells to suppress graft-vs-host disease (GVHD) was investigated. In a first model, total lymphoid irradiation (TLI)-treated BALB/C mice were given 1 mg of anti-asialo GM1 antibody. This led to the disappearance of functional suppressor cells after TLI. Injections of anti-asialo GM1 into TLI-treated BALB/C mice before infusion of 30 x 10(6) fully allogeneic (C3H) BM cells, led to a significantly decreased survival rate as compared to TLI-treated mice injected with control serum before BM transplantation (survival 29 and 83%, respectively, at 120 days after transplantation, p = 0.0032 log rank). The mortality of the former group was due to GVHD as 1 degree all dying animals showed clinical and histologic signs of GVHD, 2 degrees all animals were chimeric and 3 degrees mice receiving no or syngeneic BALB/C BM had excellent survival rates excluding BM aplasia or increased susceptibility for infections as reason for the mortality of the allogeneic BM recipients. In a second model, asialo GM1+ cells were removed in vitro from the C3H BM inoculum before injection into lethally irradiated (9 Gy) BALB/C recipients. In mice kept in specific pathogen-free conditions, this procedure resulted into a significant mortality (12/12) as compared to mice receiving BM pretreated with control serum (1/12, p = 0.0001 log rank). When kept in conventional housing, GVHD occurred in both groups but much earlier in the group receiving anti-asialo GM1-treated BM (median survival time 6 vs 46 days for the control mice, p = 0.001 log rank). No animal receiving anti-asialo GM1 and treated with syngeneic BM died, thus excluding toxicity, increased susceptibility to infections, or decreased graft take as a cause of mortality. In a last model, asialo GM1 cells were removed from syngeneic BM in a BM transplantation model in which T cell-depleted syngeneic (BALB/C) and non-T cell-depleted allogeneic (C3H) BM was administered to lethally irradiated (9 Gy) BALB/C mice. Also in this model GVHD-related mortality only occurred in the group of mice receiving syngeneic BM from which asialo GM+ cells were depleted before infusion (3/12). Our experiments thus clearly show that asialo GM1+ cells from both recipient (the TLI model) as well as donor origin (the TBI experiments) can suppress the occurrence of GVHD.

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He, Yuan, Yafei Liu, Xiao Wang, Xianyi Li, Wenle Dong, Tongrui Hao, Chenyang Zhu, Wenrong Zhou, and Zhengang Peng. "Abstract 2634: CRISPR in vivo screen utilizing removable Cas9 system to identify epigenetic immune response modulators in antigen-sensitive mouse syngeneic models." Cancer Research 84, no. 6_Supplement (March 22, 2024): 2634. http://dx.doi.org/10.1158/1538-7445.am2024-2634.

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Abstract The application of CRISPR-Cas9 screen in tumor immunology research has promoted the discovery of potential therapeutic targets and provided a deeper understanding of the mechanisms of immunotherapy resistance. Mouse syngeneic tumor model based CRISPR in vivo screen revealed significant features of immunotherapy by better approaching the tumor immune interaction. However, the immunogenicity of CRISPR-Cas9 has been widely observed in a variety of syngeneic models, which greatly limited for the application of CRISPR in vivo screen. Herein, we used two strategies for cancer cell gene editing, Cas9 protein electroporation and loxP-flanked Cas9 with Cre recombinase, to reduce the immunogenicity of CRISPR-Cas9 in CT26 subcutaneous and Renca orthotropic syngeneic models. Encouragingly, we found out that compared with constitutive Cas9-expressing All-In-One based cell pool models, both CT26 subcutaneous model and Renca orthotropic model showed a parental cell tumor comparable growth kinetics and immune checkpoint blockade ICB response by PD-1 antibody treatment. Further immuno-profiling of tumor immune microenvironment indicated limited changes from the parental cell model, which helped the data interpretation of in vivo screen outcome. We then performed a CRISPR in vivo screen by using a focused library against mouse epigenetic regulators in these two models and will discuss the hits from the screen in future. Citation Format: Yuan He, Yafei Liu, Xiao Wang, Xianyi Li, Wenle Dong, Tongrui Hao, Chenyang Zhu, Wenrong Zhou, Zhengang Peng. CRISPR in vivo screen utilizing removable Cas9 system to identify epigenetic immune response modulators in antigen-sensitive mouse syngeneic models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2634.

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Schreiber, Liesa-Marie, Carles Urbiola, Krishna Das, Bart Spiesschaert, Janine Kimpel, Fabian Heinemann, Birgit Stierstorfer, et al. "The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer." British Journal of Cancer 121, no. 8 (September 18, 2019): 647–58. http://dx.doi.org/10.1038/s41416-019-0574-7.

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Abstract Background Oncolytic virotherapy is thought to result in direct virus-induced lytic tumour killing and simultaneous activation of innate and tumour-specific adaptive immune responses. Using a chimeric vesicular stomatitis virus variant VSV-GP, we addressed the direct oncolytic effects and the role of anti-tumour immune induction in the syngeneic mouse lung cancer model LLC1. Methods To study a tumour system with limited antiviral effects, we generated interferon receptor-deficient cells (LLC1-IFNAR1−/−). Therapeutic efficacy of VSV-GP was assessed in vivo in syngeneic C57BL/6 and athymic nude mice bearing subcutaneous tumours. VSV-GP treatment effects were analysed using bioluminescent imaging (BLI), immunohistochemistry, ELISpot, flow cytometry, multiplex ELISA and Nanostring® assays. Results Interferon insensitivity correlated with VSV-GP replication and therapeutic outcome. BLI revealed tumour-to-tumour spread of viral progeny in bilateral tumours. Histological and gene expression analysis confirmed widespread and rapid infection and cell killing within the tumour with activation of innate and adaptive immune-response markers. However, treatment outcome was increased in the absence of CD8+ T cells and surviving mice showed little protection from tumour re-challenge, indicating limited therapeutic contribution by the activated immune system. Conclusion These studies present a case for a predominantly lytic treatment effect of VSV-GP in a syngeneic mouse lung cancer model.

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Narimatsu, Akitomo, Rohan Bir Singh, Pier Luigi Surico, Seokjoo Lee, Katayoon Forouzanfar, Francesca Kahale, Aytan Musayeva, Thomas H. Dohlman, Tomas Blanco, and Reza Dana. "Assessment of Corneal Graft Outcomes in a Murine Model of Endothelial Keratoplasty." Journal of Clinical Medicine 13, no. 17 (August 24, 2024): 5010. http://dx.doi.org/10.3390/jcm13175010.

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Objectives: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. Methods: We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) as donors and BALB/c mice as recipients. Slit-lamp examination and optical coherence tomography were performed for clinical evaluations for 16 weeks post-procedure. Criteria for the assessment of corneal opacity were established and the animals were graded weekly. Additionally, we assessed corneal endothelial cell density by harvesting the corneas and staining with zonula occludens-1 (ZO-1). Lastly, lymph nodes were collected, and CD4+ T cells were MACS-sorted and co-cultured with syngeneic or allogeneic antigen-presenting cells (APCs) to assess the IFN-γ expression levels by alloreactive Th1 cells (ELISPOT) in response to the direct (donor) or indirect (host) pathways of sensitization. Results: We observed graft failure in four animals, including irreversible corneal opacity, graft detachment, and anterior synechiae in the first four weeks. The remaining animals were graded between 0 and 5 as per the established criteria. The total and graft corneal thickness and endothelial cell density progressively worsened with a higher grade of corneal opacity. The direct allosensitization of Th1 cells was significantly higher in mice with a higher grade of corneal opacity. At 16 weeks follow-up, the grafts remained stable with low opacity scores in syngeneic EK recipients; however, the opacity scores were higher and variable in allogeneic EK recipients. Conclusions: These findings establish a standardized protocol to assess the graft outcomes in a murine model of EK. Furthermore, we delineate the underlying immunological pathway that contributes to the immune-mediated rejection of grafts in this model.

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Ildstad, S. T., S. M. Wren, J. A. Bluestone, S. A. Barbieri, D. Stephany, and D. H. Sachs. "Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10)." Journal of Immunology 136, no. 1 (January 1, 1986): 28–33. http://dx.doi.org/10.4049/jimmunol.136.1.28.

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Abstract Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts, whether or not the allogeneic bone marrow was T cell depleted. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. In addition, experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it. This system may be helpful as a model for the study of alloresistance and for the identification of syngeneic cell phenotypes, which when present prevent engraftment of allogeneic marrow.

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Geller, RB, AH Esa, WE Beschorner, CG Frondoza, GW Santos, and AD Hess. "Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor using cyclosporine-induced syngeneic graft-versus-host disease in the rat." Blood 74, no. 3 (August 15, 1989): 1165–71. http://dx.doi.org/10.1182/blood.v74.3.1165.1165.

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Abstract:

Abstract Lethally irradiated LouM rats reconstituted with syngeneic bone marrow and then treated with cyclosporine (CsA) for 40 consecutive days following transplant developed a graft-v-host disease (GVHD)-like syndrome after CsA cessation. This model of GVHD was used to define and characterize a graft-v-tumor (GVT) effect against a syngeneic plasmacytoma CRL1662 cell line which expresses class II major histocompatibility (MHC) antigen (Ia). Nylon wool-nonadherent spleen cells from animals who developed syngeneic GVHD were capable of significant lysis against chromium-labeled tumor target cells in a four- hour chromium released cell mediated lympholysis assay; maximum lysis occurred five days following cessation of CsA when clinical signs first appeared. Cytolytic activity declined to baseline as GVHD symptoms resolved. Fractionation of splenocytes into lymphocyte subsets demonstrated that cytolytic lymphocytes (CTLs) of the OX8 phenotype (non-helper T) were capable of significant lysis against tumor target cells. Lysis of tumor cells was blocked by preincubation with monoclonal antibodies (MoAb) specific for the rat anti-class II MHC antigen but not with MoAb against class I. Incubation of tumor cells with gamma-interferon increased expression of tumor class II MHC antigens and significantly increased their susceptibility to lysis by nylon wool-nonadherent splenocytes from animals with syngeneic GVHD. These studies have demonstrated an in vitro GVT of syngeneic GVHD against an Ia-bearing tumor; the effector cell is a CTL of the OX8 phenotype specific for the class II MHC antigen.

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Journal articles on the topic 'Syngeneic model'

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