Dissertations / Theses: 'Human monoclonal antibodies (humAbs)'

1

Austin, Eric B. "Human monoclonal antibodies." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276187.

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2

Ohlin, Mats. "Human monoclonal antibody technology a tool to investigate human antibody repertoires /." Lund : Dept. of Immunotechnology, Lund University, 1992. http://catalog.hathitrust.org/api/volumes/oclc/39693827.html.

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3

Watson, Nigel. "Monoclonal antibodies to human immunoglobulin allotypes." Thesis, University of Strathclyde, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304897.

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4

De, Silva M. G. "Human monoclonal antibodies in the study of diabetes." Thesis, University of Surrey, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233146.

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5

Bell, Graham Thomas. "Studies on the production of human monoclonal antibodies." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/19241.

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6

Heath, Lindsay Anne. "Heterogeneity in neural crest development detected by monoclonal antibodies." Thesis, University of Southampton, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293618.

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7

Hunter, Nicole Marie. "A system for the production of human monoclonal antibodies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0006/MQ46024.pdf.

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8

Johansson, Daniel X. "Expression and interaction studies of recombinant human monoclonal antibodies /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-137-1/.

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9

Bindon, Carol Ianthe. "Complement-mediated lysis by monoclonal antibodies for human therapy." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253842.

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10

Soos, M. A. "Studies with monoclonal antibodies to the human insulin receptor." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373704.

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11

Thompson, K. M. "The production of human monoclonal antibodies from autoimmune patients." Thesis, University of Bath, 1986. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356846.

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12

Ribeiro, Maricy Alves. ""Contribuição ao imunodiagnóstico da leptospirose humana: ênfase ao uso de anticorpos monoclonais"." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-15032004-161427/.

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A prova sorológica de referência na leptospirose ainda é a soroaglutinação microscópica (SAM). Devido à complexidade desta prova avaliamos alguns testes rápidos para triagem dos anticorpos anti-leptospiras na fase aguda da infecção. Na década de 80, uma hemaglutinação passiva, utilizando frações polissacarídicas de leptospiras, foi considerada apropriada ao diagnóstico precoce, porém esta preparação antigênica incluía muitos antígenos comuns reconhecidos por anticorpos de 4% dos indivíduos normais. Um novo ELISA (enzyme-linked immunosorbent assay) utilizando uma suspensão de antígenos imunodominantes, resistentes à proteinase K, foi padronizado e avaliado quanto ao seu valor diagnóstico. Com 89,9% de sensibilidade e 97,4% de especificidade, esta técnica, referida como PK-ELISA, satisfaz os requisitos necessários para as provas de triagem da leptospirose humana. No entanto, em virtude de alguns reagentes usados nesta preparação antigênica serem importados e muito instáveis, foi proposta a introdução de novos métodos empregando-se anticorpos monoclonais. Em um Acordo de Pesquisa Cooperativa entre o Instituto Adolfo Lutz e o Laboratório Fleury foram produzidos hibridomas contra leptospiras. Dois deles foram selecionados para dar continuidade ao estudo: um, secretando anticorpos monoclonais (AcM) para um epítopo detectado em 16 de 23 sorovares do gênero Leptospira mais freqüentes em nosso meio (clone A12P4), e outro específico a somente um sorogrupo patogênico, icterohaemorragiae (clone H7P1). O AcM A12P4, uma imunoglobulina G2B (IgG2B), reagiu com epítopo presente nos componentes de pesos moleculares (PM) de 16-18 kDa dos lisados de leptospiras das cepas RGA e M-20, quando separados na eletroforese em gel de poliacrilamida, e com componentes de PM de 75-84kDa dos sorovares copenhageni e canicola. Por sua vez, o AcM H7P1, uma imunoglobulina G, reagiu com um epítopo comum a várias frações de PM acima de 21 kDa da cepa RGA e com componentes de PM de 21-22 kDa e de 75-82 kDa da cepa M-20. Os monoclonais foram empregados em provas imunoenzimáticas para a detecção de anticorpos específicos em amostras séricas pareadas coletadas de 52 pacientes com leptospirose, e do grupo controle que incluiu amostras séricas de 57 pacientes com outras doenças consideradas no diagnóstico diferencial, e de 68 indivíduos normais. Estas provas, no entanto, não foram satisfatórias. Finalmente, um novo ELISA foi desenvolvido no presente estudo que utiliza a suspensão de antígenos AgMc, purificados por cromatografia de afinidade utilizando a Sepharose 4B ativada com CNBr acoplada aos anticorpos monoclonais descritos acima. Os resultados obtidos com esta prova foram comparados aos obtidos com outros testes disponíveis em nosso meio, como a SAM e o ELISA clássico (ELISA c). Este novo método, o ELISA AgMc, com 80,70 % e 83,33 % de sensibilidade e especifidade, respectivamente, em relação à SAM; valores preditivos positivo e negativo de 69,70% e 90,10% respectivamente e índice de concordância geral de 82,49%, não parece ser um protocolo promissor para o diagnóstico rápido na leptospirose humana. Além disso, tomando-se a SAM como diagnóstico verdadeiro, os resultados obtidos no novo teste, após a conclusão diagnóstica do grupo de pacientes com a leptospirose, mostrou uma discordância significativa. São discutidas as possíveis explicações para os resultados encontrados.
The best serological test for leptospirosis laboratory diagnosis remains the microscopic agglutination test (MAT). Because of the complexity of MAT, we have been developed some rapid screening tests for leptospiral antibodies detection in the acute phase of infection. In the decade of 80, a passive hemagglutination test employing polysaccharide fractions of leptospires was considered appropriate for early diagnosis, but its antigen preparation included common antigens recognized by antibodies from 4% of healthy individuals. A new ELISA (enzyme-linked immunosorbent assay) employing proteinase K resistant immunodominant antigens was developed and its potential diagnosis evaluated. This technique, the PK-ELISA, presented 89.9% sensitivity and 97.4% specificity, and satisfied the requeriments needed for serological screening tests of human leptospirosis. However, some of the reagents used in its antigen preparation are imported and very unstable. So, it was proposed, in a Cooperative Research Accordance between Instituto Adolfo Lutz and Laboratório Fleury, to try new approaches with monoclonal antibodies. Two hibridomas secreting specific monoclonal antibodies (MAb) were selected: one, against an epitope detected in 16 of 23 members of the genus Leptospira (clone A12P4) and the other, specific to the icterohaemorragiae serogroup (clone H7P1). The MAb A12P4, a G2 (IgG2B) immunoglobulin, reacted with an epitope present in the 16-18 kDa components of icterohaemorragiae serogroup and with the 75-84 kDa components of serovars copenhageni and canicola, after whole-cell lysates of the leptospires were separated by sodium dodecyl sulfate- polyacrylamide gel electrophoresis. The MAb H7P1, which is an IgG, reacted with an epitope common to several fractions of molecular weight above 21 kDa of strain RGA and with the 21-22 kDa and the 75-82 kDa components of strain M-20. Both monoclonal antibodies were employed in enzyme immunoassays for detecting specific antibodies in serum samples serially colleted from 52 patients with leptospirosis, and from the control group, which consisted of sera from 57 patients with other diseases included in the differential diagnosis, and from 68 healthy individuals. These tests, however, were not satisfactory. A new ELISA was developed in the present study employing an antigen suspension AgMc, purified by affinity chromatography with CNBr-activated Sepharose 4B coupled to the monoclonal antibodies described above. The results obtained with this test were compared to the MAT and to the classical IgM ELISA (ELISA c). The new method, AgMc ELISA, presented serological indices, relatively to reference test MAT, of 80.70 % and 83.33 % of sensitivity and specificity, respectively; positive and negative predictive values of 69.70 % and 90.10 %, respectively, and general agreement index of 82.49 %. So, this test was not considered a promising approach to rapid diagnosis of human leptospirosis. Moreover, the proportion of patients diagnosed as having leptospirosis by the AgMc ELISA and the MAT differ significantly. The possible explanations for the results obtained are discussed.

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13

陳榮宗 and Wing-chung Chan. "The production and use of monoclonal antibodies to human leukocytes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1988. http://hub.hku.hk/bib/B3198129X.

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14

Wei, Jiewei School of Biotechnology &amp Biomolecular Science UNSW. "Construction, expression and characterisation of a human anti-CD48 monoclonal antibody." Awarded by:University of New South Wales. School of Biotechnology and Biomolecular Science, 2006. http://handle.unsw.edu.au/1959.4/27413.

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Monoclonal antibodies and antibody-based entities are a major class of therapeutic proteins. The surge in development of monoclonal antibodies is predominantly due to the utilization of technologies for producing fully human antibodies, namely phage display and transgenic mice with human humoral immune systems. Human CD48, a cell-surface adhesion molecule, is a potential tumor target for the treatment of white blood cell malignancies, principally leukemia and lymphoma. A truncated, secreted form of CD48 was expressed in CHO cells, and was shown to bind to existing anti- CD48 murine antibodies. A human anti-CD48 scFv antibody fragment, (designated scFv-N2A) was previously isolated using phage display technology from a synthetic human scFv immunoglobulin gene library. The scFv-N2A was reassembled as a human IgG1 monoclonal antibody (designated IgG1-N2A), expressed in CHO cells and the binding of IgG1-N2A to recombinant CD48 was confirmed by enzyme-linked immunosorbent assay, surface plasmon resonance and fluorescence activated cell sorting. IgG1-N2A binding to CD48 on Raji cells showed that the specificity of the human antibody for GPI-linked CD48 was conserved. In biological studies using a human lymphoma cell line (Raji), it was found that the IgG1-N2A antibody was able to induce potent growth inhibition, with a 68% reduction in viable cells. Furthermore, Raji cells treated with IgG1-N2A showed evidence of increased ethidium bromide uptake and cell shrinkage, which are characteristics associated with direct induction of apoptosis. The data suggests the novel human anti-CD48 IgG1-N2A monoclonal antibody can block proliferation and promote apoptosis of lymphoma cells, and therefore has potential as a lead antibody candidate for the treatment of white blood cell malignancies.

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15

Ejtehadian, Tahereh. "Generation of anti-human apolipoprotein E isoform-specific monoclonal antibodies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq20971.pdf.

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16

Durko, Margaret. "Identification of human organ-specific cancer neoantigen by monoclonal antibodies." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75432.

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Soluble lung tumor antigen activity, as determined by the leukocyte adherence inhibition (LAI) assay, was enriched by physicochemical methods from chemically-defined spent medium of a lung cancer cell line (NCI-H69). To identify the polypeptide carrying the antigenic determinant, BALB/c mice were immunized with the enriched isolate and their splenic lymphocytes were fused with mouse plasmacytoma cells.
Eight hybrids were cloned and produced MAbs that immunoprecipitated principally a single chain of MW 40,000 (p40) as well as minor chains of MW 25,000 (p25) and MW 13,000 (p13) which were probably degradation products of p40. On 2D gels, p40 was composed of 7 spots with a pI of 6.1 to 7.6, which was not altered by neuraminidase digestion. Affinity chromatography with MAb anti-p40 absorbed p40 and LAI activity. The bound and recovered fraction was enriched for p40 and LAI activity. Affinity-purified p40 contained the previously identified p25 and p13 as well as a MW 32,000 polypeptide (p32). MAb anti-p40 was directed to a common framework determinant on p40 since MAb anti-p40 bound to cancer cells from other organs. The lung cancer organ-specific determinant recognized by leukocytes from lung cancer patients was not recognized by the MAb. Affinity purified p40 triggered the LAI response for leukocytes from patients with lung cancer but not for leukocytes from control subjects or patients with colon cancer or malignant melanoma in blind testing. Partial cross-reactivity was observed with leukocytes from patients with breast cancer. Thus, a p40 molecule has been purified that is expressed on the membranes of lung cancer cells and triggers immunologically-mediated LAI.

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17

Dan, Michael. "Human anti-glioma monoclonal antibodies from patients with neurological tumors." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74367.

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The current management of malignant gliomas is unsatisfactory compared to other solid tumors. Expected median survival is less than one year with even the best of care. At some point in their illness, most patients with neurological tumors are capable of mounting an immune response to their disease. This study focused on the humoral immune response of brain tumor patients by preparing human-human B cell hybridomas from autologous peripheral blood lymphocytes and a human myeloma-like cell line, designated as TM-H2-SP2. Eighteen fusions were successfully performed, and 15.8% of all microwells screened contained human immunoglobulin with anti-tumor activity. Five hybridomas, designated as BT27/1A2, BT27/2A3, BT32/A6, BT34/A5, and BT54/B8 were selected for detailed study. All five produced monoclonal IgM in a range of 2.4-44 $ mu$g/ml, had a similar (but not identical) pattern of reactivity against a panel of human tumor cell lines, and did not react with normal human astrocytes. All five human monoclonal antibodies (HmAbs) recognized a subpopulation of tumor cells based on multiparameter flow cytometric studies. Cell sorting experiments suggested that the identified subpopulation may share certain properties with hypothetical tumor stem cells. Preliminary antigen characterization indicated that the HmAbs are directed to cell surface glycolipids. These HmAbs possess certain properties of reactivity that suggest potential roles for them in the future diagnosis and clinical management of human malignant gliomas.

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18

Bolt, Sarah Louise. "Serotherapy with monoclonal antibodies directed to the human CD3 antigen." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240125.

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19

Rahman, Mohammed Abbas Anisur. "Molecular properties of human monoclonal anti-DNA and antiphospholipid antibodies." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286156.

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20

Ehrenstein, Michael Randolph. "Production and analysis of human monoclonal IgG anti-DNA antibodies." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309101.

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21

James, Ian Edward. "The production and characterization of human osteoclast-reactive monoclonal antibodies." Thesis, University of Bath, 1992. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303100.

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22

MacIntyre, Elizabeth A. "Activation of human haemopoietic cells via Fc receptors for IgG." Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241359.

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23

Darsley, M. J. "Studies on the interaction of monoclonal antibodies with antigens of biological interest." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354824.

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24

Fiddes, Jane L. Sutton Biotechnology &amp Biomolecular Sciences Faculty of Science UNSW. "Development of recombinant human monoclonal antibodies suitable for blood grouping using antibody engineering techniques." Awarded by:University of New South Wales. Biotechnology & Biomolecular Sciences, 2007. http://handle.unsw.edu.au/1959.4/40503.

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Transfusion medicine is an important part of modern health care and the provision of reliably phenotyped red blood cells (RBC) is essential for safe and effective blood transfusions. For identification of many RBC antigens, monoclonal antibodies of either murine or human origin are available for use in agglutination assays, in which they perform as well as or better than the human polyclonal antibody preparations which they have replaced. However, the detection of some blood groups is still reliant on the use of human polyclonal antisera, which is a less reliable reagent source with respect to availability, batch to batch variation and bio-safety. The use of recombinant antibody and phage display technology for the discovery of new monoclonal antibodies with specificity for some of these RBC antigens has the potential to deliver an economical, unlimited supply of specific antibody reagents suitable for use in RBC phenotyping. Samples of human B cells from donors producing useful phenotyping antibodies were identified and transformed using Epstein Barr virus into lymphocyte cell lines. Antibody genes were obtained from the cell lines in the form ofRNA which was reverse transcribed, amplified by PCR and cloned into a phagemid vector system to generate several combinatorial antibody libraries. These antibody libraries were displayed on the surface of phage particles and subjected to antigen-driven selection by several rounds of phage display biopanning using soluble and cell based RBC antigens. In addition a large naIve library was biopanned against the same antigens in an attempt to isolate a wide range of antibodies suitable for blood typing. Several high quality combinatorial antibody libraries with respect to size (> 107 clones) and diversity were generated. Biopanning of recombinant libraries resulted in enrichment of phage antibodies specific for RBC antigens, and several clones were isolated which were shown to be specific for Duffy a antigen. The isolated antibodies would be ideal candidates for re-engineering into multivalent antibody molecules capable of direct agglutination of RBC and as such, have the potential to replace human polyclonal sera in the identification of Duffy a RBC antigen phenotyping.

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25

Chin, Li-Te. "Site-directed in vitro immunization a model of sequential antigen-specific activation of human B cells /." Lund : Dept. of Immunotechnology, Lund University, 1994. http://books.google.com/books?id=S89qAAAAMAAJ.

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26

Cottingham, Janet Denise. "Isolation of anti HIV 1 human monoclonal antibodies from vaccinated individuals." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249208.

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27

Buckle, Clive. "Production of human monoclonal antibodies to ovarian carcinoma using phage display." Thesis, University of Sheffield, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.541444.

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28

Thomas, Myles Duncan. "Production and characterisation of novel human monoclonal antibodies against malignant melanoma." Thesis, University of East London, 1995. http://roar.uel.ac.uk/1275/.

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Malignant melanoma is an immunogenic tumour capable of inducing a humoral immune response, as shown by tumour-reactive serum antibody in patients. Lack of effective chemotherapy in association with the immunogenic nature of the malignancy, has stimulated interest in the immunological management of the malignancy by antibody. Many mouse monoclonal antibodies against melanoma antigens have been developed, and some have been shown to induce tumour regression. However, a limitation on the use of mouse monoclonal antibodies in patients is the induction of an immune response against the immunising xenogeneic protein. The employment of human monoclonal antibodies, may be expected to reduce the patient's immune response against the allogeneic protein. Although more difficult to produce than mouse monoclonal antibodies, several human monoclonal antibodies have been established which induce tumour regression. Here I describe the establishment of mouse/human heterohybridomas producing human monoclonal antibody, from tumour-draining lymph nodes. A series of novel assay systems, initially developed and characterised using melanoma reactive mouse monoclonal antibodies, were sequentially employed for the selection of human antibody exhibiting high tumour specificity. Several clones producing melanoma reactive human antibody were established. Clone MDT. 1 was selected for further characterisation, because of its highly selective reactivity against viable melanoma and other neuroectodermal cell lines, but lack of reactivity against other common malignant and non-malignant cell lines. Such restricted cell reactivity is characteristic of reactivity with class 2 tumour associated antigens. MDT. 1 was shown, in ELISA, to exhibit reactivity to ganglioside antigens GD3, GD2, GD1b, GM3 and GM2. These antigens are commonly associatedw ith the malignant transformation of melanocytes and other neuroectodermal cells. Enzymatic modification of GM3, with neuraminidase, identified the reactive minimal essential epitope as Neua2- 3Galß1-4GIc-. Reactivity with rat monoclonal antibody 9G4 and molecular analysis showed MDT. 1 is encoded by the highly conserved VH4 gene, VH4-21. Like other VH4-21 encoded autoantibodies MDT. 1 exhibits reactivity with the cold agglutinin T. Analysis of the structures of `i' and sialogangliosides has identified similar structural epitopes, which may confer MDT. 1 reactivity. VH4-21 encoded autoantibody 216 exhibits similar reactivity with tumour associated ganglioside antigens as MDT. 1. Sialo-ganglioside/`i' reactive VH4-21 encoded antibodies, could therefore represent an important aspect of autoantibodies in the overall host immune response to tumour.

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29

Rijal, Pramila. "A study of human monoclonal antibodies to Influenza and Ebola viruses." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:ce156cca-cc96-407a-8a3f-779e5c25f445.

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This thesis describes an analysis of the B cell repertoire in humans in response to infection or vaccination with Influenza or Ebola. We isolated monoclonal antibodies (mAbs) from individuals using single B cell cloning and PCR technology, and defined their epitopes, binding characteristics and neutralisation properties. As summarised by Thomas Francis in 1960, we found that the secondary B cell response to Influenza is largely determined by the primary response to the virus that the donor was exposed to in childhood. In some individuals this can lead to focusing of the polyclonal antibody response to a single site on the influenza haemagglutinin. Monoclonal antibodies isolated from such focused responses selected escape mutations in vitro that matched actual antigenic drift observed in circulating viruses. Recapitulation of antigenic drift in vitro with human mAbs, in parallel with standard analysis with ferret anti-sera, may contribute to improved selection of vaccine strains by the WHO. A second consequence of preferential selection of B cell responses from memory cells laid down early in life, is the expansion of broadly cross-reactive clones during exposures to viruses that are only distantly related to the original stimulus. We have isolated many protective antibodies to conserved epitopes on both haemagglutinin and neuraminidase from individuals with appropriate exposure histories. One novel antibody binds to the conserved active site of neuraminidase. Antibodies of this type may have therapeutic potential to complement antibodies to the conserved stem of Haemagglutinin. In contrast to Influenza, the antibody response to the Ebola glycoprotein (GP) in vaccinated humans was essentially primary. The elicited antibodies were closer in sequence to germline than those to Influenza, and contained fewer somatic mutations. The response was more diverse, employing a wide selection of VH/L genes, and was directed at multiple epitopes in at least three distinct regions on the GP. Despite these features, half of the antibodies neutralised an Ebola surrogate virus in vitro, and many were therapeutic in a murine infection model. We developed a cocktail of antibodies to three non-overlapping sites for testing as a therapy in a stringent model of Ebola infection in the guinea pig. Taken together our results fit with a Darwinian model of selection of the fittest B cells in the germinal centre reaction, where memory cells have a selective advantage over naïve B cells.

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30

Stewart, Keith N. "Production and characterisation of monoclonal antibodies to human glomerular mesangial cells." Thesis, University of Aberdeen, 1993. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU539718.

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Glomerular mesangial cells are involved in a number of renal diseases and their response to glomerular hyperfiltration appears to be the final common pathway for progression of renal failure of diverse etiology. It is the mesangial cell which, in response to various mediators, proliferates and increases synthesis of mesangial cell matrix. This may result in the destruction of the glomerular space and may lead to end-stage renal failure. The main aim of this study was, therefore, to produce monoclonal antibodies to human mesangial cells, allowing better characterisation of these cells. Human glomerular cell cultures were successfully established, and pure mesangial cells obtained, these were used to immunise mice. Using standard hybridoma techniques, as well as the development of a novel mesangial cell micro-ELISA allowed the production of 29 antibodies to human glomerular mesangial cells. These antibodies showed minimal reactivity against normal and neoplastic leucocytes but had a greater reactivity with adherent cell lines. Fourteen out of 18 'acetone fast' antibodies were found to react with various cells and structures on normal kidney, six out of 14 of these reacted with mesangial cells on kidney sections. One of these monoclonal antibodies (F2.18) was characterised in more detail. Evidence from biochemical, immunochemical and functional studies revealed that this antibody was binding to a common determinant on the 1 and 2 chains of the VLA-1 family of cell surface matrix receptors. This is the first description of a monoclonal with such reactivity. Finally, the distribution of the different chains of the VLA-1 family was studied both on cultured glomerular mesangial and epithelial cells as well as on normal kidney sections. This is the first report of the production of monoclonal antibodies to purified glomerular mesangial cells. It is hoped that further characterisation of these antibodies will provide useful reagents for the study of the role of glomerular mesangial cells in the pathogensis of glomerulonephritis.

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31

Barnes, Tristan Stuart. "The generation and characterisation of monoclonal antibodies to human cytochrome P450." Thesis, University of Aberdeen, 1987. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU499831.

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(1) Ten monoclonal antibodies have been raised against human hepatic microsomal proteins, seven of which recognised a purified human liver cytochrome P450, P450hA7. (2) Two of the seven anti-P450hA7 monoclonal antibodies, when blotted against control and induced rat liver microsomes, recognised a male-specific, weakly expressed constitutive protein that showed marked induction by pregnenolone-16-carbonitrile (PCN) but not by phenobarbitone (PB). No such P450 has been previously reported. (3) Another of the anti-P450hA7 monoclonal antibodies recognised a protein that was not expressed in control, male or female, rat liver microsomes but was strongly expressed in both PCN- and PB-induced microsomes. This protein may correspond to cytochrome P450PCN1 which exhibits identical induction characteristics. (4) A third rat protein, strongly and constitutively expressed in male liver microsomes, is recognised by other anti-P450hA7 antibodies. This protein may be induced by PCN. (5) The hepatic microsomal level of immunoreactive P450hA7 in fifteen adult individuals showed marked interindividual variation and was approximately ten times higher in an epiletic chronically treated with the drugs PB, phenytoin, carbamazipine and valproate. (6) Foetal human liver microsomes contained a protein that was immunochemically similar, but not identical, to adult P450hA7. The foetal protein exhibited a slightly greater molecular mass than the adult form. The switch from the foetal to the adult form of P450hA7 occurred shortly after birth. (7) P450hA7 was immunochemically detected in HEP G2 human hepatoma cells. The cytochrome was constitutively expressed being present in cells treated with PB, PCN and benzanthracene as well as untreated cells. (8) The anti-P450hA7 antibodies have been put to a variety of applications including the immunohistochemical localisation of cytochrome P450hA7 in human tissue and the screening of human hepatic cDNA libraries in gtll. (9) These monoclonal antibodies constitute a precise and powerful tool for the further characterisation of the human cytochromes P450.

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32

Hutyuu, Hidetaka. "STUDIES ON THE UTILIZATION OF MONOCLONAL ANTIBODIES AGAINST HUMAN SERUM ALBUMIN." Kyoto University, 1997. http://hdl.handle.net/2433/202413.

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Kyoto University (京都大学)
0048
新制・論文博士
博士(農学)
乙第9604号
論農博第2138号
新制||農||746(附属図書館)
学位論文||H9||N3062(農学部図書室)
16496
UT51-97-H441
(主査)教授安本教傅, 教授井上國世, 教授森友彦
学位規則第4条第2項該当

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33

Banner, Steven John. "The expression of glutamate transporter proteins in the human central nervous system." Thesis, University of Newcastle Upon Tyne, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311941.

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34

Taylor, Vanessa Claire. "Biology of the CD52 antigen, a major glycoprotein of human lymphocytes." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242883.

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35

Kerr, Lorraine Elizabeth. "Characterization of antigens on the surface of human spermatozoa using monoclonal antibodies." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/26658.

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A panel of murine monoclonal antibodies was raised against human sperm plasma membrane in order to identify and characterize molecules important in fertilization. Twelve monoclonal antibodies were produced and of these nine belong to the IgM subclass while the remaining three are of the IgG_2a subclass. The antibodies were purified from bulk culture supernatants using affinity chromatography - the IgG antibodies on a protein A column and the IgMs on a column made using a commercially available anti-mouse IgM antibody coupled to an inert support. These purified antibodies were then used to characterize their respective antigens biochemically and assessed for their biological activity using a variety of in vitro tests of sperm function. All twelve antibodies recognized a molecule which was present on the entire surface of human spermatozoa. Eight antibodies cross-reacted with both marmoset and boar spermatozoa as well as with human leucocyte subclasses. The other four immunoglobulins were highly specific for human sperm cells and did not cross-react with any of the other cells tested. In western blotting experiments, the monoclonals recognized epitopes present on a variety of molecules. Only one antibody, spm 4/4, failed to recognize any proteins when transferred to nitrocellulose. When tested for their ability to interfere with the acrosome reaction, four antibodies significantly inhibited the percentage of spermatozoa in a population undergoing a sponataneous acrosome reaction. Subsequently, two of these antibodies, spm 1/1 and spm 1/2, were shown to cause a significant decrease in the percentage of sperm which were induced to undergo the acrosome reaction by the calcium ionophore A23187. The interaction between spermatozoa and the zona pellucida was assessed using salt-stored human zonae and two immunoglobulins, spm 1/2 and spm 4/6, significantly reduced the mean number of sperm bound to the zona pellucida. These two antibodies also caused a marked inhibition of sperm-oolemmal fusion as assessed using the hamster egg penetration test. When this test was performed at various sperm concentrations, both of these antibodies exhibited a dose dependent decrease in the penetration rate. One further antibody, spm 4/7, was found to have biological activity in that it stimulated the interaction between sperm and the oolemma.

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36

Chi, Linda Shu-Yun. "Generation and study of genetically engineered human monoclonal antibodies against HIV-1." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388629.

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Robinson, Mark James. "The development of monoclonal antibodies towards the glycoproteins of the human pneumoviruses." Thesis, University of Newcastle Upon Tyne, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533698.

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38

Higgins, R. M. "The production and characterization of monoclonal antibodies against human lymphocyte surface antigens." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604039.

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39

Kumar, Arvind. "Studies of the conserved neutralising epitopes of human rhinoviruses using monoclonal antibodies." Thesis, University of Surrey, 1989. http://epubs.surrey.ac.uk/941/.

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Armour, Kathryn L. "A study of the properties of monoclonal antibodies against human cardiac troponin I." Thesis, University of Aberdeen, 1993. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=202371.

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i) Human cardiac cDNA libraries were constructed and clones encoding human cardiac troponin I (cTnI) isolated. ii) Both the entire cTNI cDNA and a 5'-portion, were expressed in Escherichia coli as fusion products with β-galactosidase. The full-length cDNA was also expressed unfused. iii) The murine monoclonal antibody 29Mu is specific for human and baboon cTnI whereas the 31Mu antibody reacts with cTnI from a range of species. These antibodies might be useful in the imaging of necrotic cardiac tissue. In this study, 31Mu was found to bind to all prepared forms of cTnI antigen, in enzyme-linked immunosorbant assays (ELISAs) and, where tested, in Western blots. Thus, its epitope is localised towards the N-terminus of cTnI. 29Mu bound to the bacterially-produced unfused cTnI but not to the fusion polypeptides or crude bovine cTn. Its ability to bind to human cardiac extracts was related to the method of their preparation, indicating that the epitope of 29Mu shows greater conformational dependency than that of 31Mu. iv) cDNAs encoding the variable domains of 29Mu and 31Mu were cloned and chimaeric antibodies, comprising murine variable and human constant regions produced. Humanised antibodies, in which only the antigen-binding sites were of murine origin, were also produced. Such recombinant antibodies would be expected to exhibit reduced immunogenicity in man. v) Neither the chimaeric nor humanised antibody versions of 29Mu bound cTnI. Chimaerised 31Mu reacted with all forms of cTnI but did not show complete equivalence to 31Mu. An antibody containing the humanised 31 kappa chain and the chimaeric heavy chain was reactive to all forms cTnI in ELISAs but its efficiency of binding, relative to that of the chimaeric antibody, was dependent upon the antigen source. Humanised heavy chains were produced utilising two different human frameworks and the framework, showing closer homology to the 31Mu variable domain, supported antigen binding with fewer murine residue substitutions. However, both successful humanised 31 antibodies showed some cross-reactivity.

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41

ANDREANO, EMANUELE. "A NOVEL APPROACH TO UNRAVEL THE RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F-PROTEIN FUNCTIONAL ANTIBODY REPERTOIRE IN ADULT HEALTHY DONORS." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1071780.

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Respiratory syncytial virus (RSV) is the chief cause of low respiratory tract infection deaths in infants under 5 years of age. Since no vaccine is currently available, novel approaches are needed to support the development of new candidates. Herein, elements of the “Reverse Vaccinology 2.0” approach were used to unravel functional, genetic and structural features that characterize the effective adult human antibody response to RSV infection. The data presented in this thesis show that the majority of identified neutralizing antibodies (nAbs) recognize both RSV F-protein conformations (cross-binders) even if a preferential binding towards the prefusion (preF) was observed. Furthermore, the IGHV1 gene family was identified as predominant in the functional antibody response, despite different heavy chain gene rearrangements seem to better recognize specific epitope regions on the preF. Moreover, predominant gene derived-nAbs, showing high neutralization potency, were found to specifically recognize a defined epitope region placed between Site Ø, Site II and Site V on the preF surface. Finally, the co-crystal structure of preF bound to Pl2_E08, a predominant gene derived nAb belonging to the IGHV1-69 gene family, was determined. Structural data confirm what was previously observed in a competition assay and reveal an important epitope region that could play a pivotal role in eliciting nAbs against different RSV A strains and even human metapneumovirus (MPV). These findings identify a specific site of pathogen vulnerability and highlight the possibility to design novel strategies to target and expand predominant gene derived-nAbs. This approach could result in high protection against RSV and consequent reduction of the high burden brought by this pathogen.

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McEvoy, Fintan John. "An evaluation of models used in study of monoclonal antibodies against human fibrin." Thesis, Royal Veterinary College (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522687.

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43

Shan, Daming. "Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/5682.

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44

Al-Fadhli, Suad M. "Characterization of site-directed monoclonal and polyclonal antipeptide antibodies to human estrogen receptor." Thesis, Boston University, 1994. https://hdl.handle.net/2144/37996.

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Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Monoclonal and polyclonal antibodies were developed against a synthetic peptide derived from a sequence in the A/B transactivation domain (residues 140-154) of the human estrogen receptor (hER). These antibodies were characterized with respect to site specificity, receptor specificity and species specificity and ability to bind to the van ous receptor forms. The antibodies were site specific since binding to estrogen receptor (ER) was displaced with the free peptide. The antibodies did not recognize progestrone, and androgen receptors. The antibodies cross-reacted with the ER from calf, rat and mouse uteri and human breast tumors, suggesting that the epitope for these monoclonal antibodies (MAbs) is conserved among vanous spectes. The interaction of the antibody with the functional estrogen receptor has been characterized by sucrose density gradient analysis. The MAbs did not recognize the molybdate-stabilized, untransformed, oligomeric (8S), suggesting that this epitope may be masked by interaction with heat shock proteins or conformationaly inaccessible. The antibodies reacted with the activated (4S) and the transformed (5S) forms of the ER, suggesting that the epitope is accessible in the 4S and the 5S forms of the ER and that dimerization of the 4S ER into 5S ER does not interfere with the epitope accessibility. Immunoblot analysis using polyclonal and monoclonal antibodies demonstrated cross-reactivity with a 55 kDa nuclear protein (NP55). This protein was detected only in the nuclear-KCI extracts but not the cytosolic extracts . It lacked estradiol binding activity, and is expressed in steroid-hormone target tissues from different species. This protein was also detected in some ER positive human breast tumors but was not detected in ER negative tumors. This protein (NP55) was not detected with polyclonal or monoclonal anti bodies developed against different regions of the ER, indicating that it is not a proteolyzed form of the ER. The availability of site-directed antibodies to ER-functional domains represent a valuable tool, particularly, m studying ER in its different forms, and in the analyses of the structural integrity of human breast tumor estrogen receptors. The observation that one of these antibodies recognizes a umque nuclear protein may prove useful to identify this ER-related protein.
2031-01-01

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45

Aversa, Gregorio Giuseppe Gerardo. "Production and characterization of monoclonal antibodies to human activation and memory T cell antigens." Thesis, The University of Sydney, 1990. http://hdl.handle.net/2123/18628.

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46

Shearer, M. A. "Monoclonal antibodies to human interferon-#alpha# applied to the study of interferon-receptor interaction." Thesis, Open University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379866.

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Parsons, Stephen Frederick. "The use of monoclonal antibodies to study the components of the human erythrocyte membrane." Thesis, Open University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278501.

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Yuan, Tingting, and 袁婷婷. "Identification of intermediate antibodies of broadly neutralizing HIV-1 human monoclonal antibody b12 and characterization of variable loops of HIV-1 envelop glycoprotein." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196445.

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Sun, Qiyu. "Human GM-CSF, IL-3 and IL-5 receptor expression and their functional domains studied with monoclonal antibodies /." Title page, contents and abstract only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phs9569.pdf.

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Corti, Davide. "Analysis of the human B cell memory repertoire against infectious pathogens and isolation of broadly neutralizing human monoclonal antibodies /." Bern : [s.n.], 2008. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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Dissertations / Theses on the topic 'Human monoclonal antibodies (humAbs)'

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