Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin
Thesis (Ph.D.)--Memorial University of Newfoundland, 1993. Medicine Bibliography: leaves 250-275 The objective of this project was to produce bispecific monoclonal antibodies (BsMabs) which recognise both the tumour associated carcinoembryonic antigen (CEA) and the chemotherapeutic agent doxorubicin...
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ftmemorialunivdc:oai:collections.mun.ca:theses3/80389 2023-05-15T17:23:32+02:00 Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin Reddy, Vijay Subba, 1961- Memorial University of Newfoundland. Faculty of Medicine 1993 xvii, 275 leaves : ill. Image/jpeg; Application/pdf http://collections.mun.ca/cdm/ref/collection/theses3/id/80389 eng eng Electronic Theses and Dissertations (32.18 MB) -- http://collections.mun.ca/PDFs/theses/Reddy_VijaySubba.pdf 76165746 http://collections.mun.ca/cdm/ref/collection/theses3/id/80389 The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries CEA (Oncology) Monoclonal antibidies Text Electronic thesis or dissertation 1993 ftmemorialunivdc 2015-08-06T19:18:37Z Thesis (Ph.D.)--Memorial University of Newfoundland, 1993. Medicine Bibliography: leaves 250-275 The objective of this project was to produce bispecific monoclonal antibodies (BsMabs) which recognise both the tumour associated carcinoembryonic antigen (CEA) and the chemotherapeutic agent doxorubicin, as a complementary approach to the use of immunoconjugates for site specific drug delivery. A monoclonal anti-CEA hybridoma (11-285-14) was made sensitive to hypoxanthine, aminopterin and thymidine (HAT) , by back selecting it in increasing concentrations of 8- azaguanine. Eight 8-azaguanine resistant fusion partners were selected based on growth characteristics and continued anti- CEA production. As doxorubicin (Dox) is a hapten, it was conjugated to carrier proteins keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA) using l-ethyl-3- (dimethyl-aminopropyl) carbodiimide. Dox-KLH arid Dox-BSA conjugates were employed to immunize mice and spleen cells were used for fusions with the HAT sensitive anti-CEA 11-285-14 using standard hybridoma procedures. Enzyme linked immunosorbent assays (ELISAs) were developed to test the hybrids obtained for anti-CEA, anti-Dox, anti-BSA and dual bispecific activity. Sixteen fusions from Dox-KLH immunized mice yielded 621 hybrids of which 47 showed low level bispecificity. Eight fusions with Dox-BSA immunized mice yielded 297 hybrids. Hybrids showing dual activities were cloned and 7 out of 286 of the positive clones have been selected for expansion. Thesis Newfoundland studies University of Newfoundland Memorial University of Newfoundland: Digital Archives Initiative (DAI) Keyhole ENVELOPE(-67.338,-67.338,-68.785,-68.785) |
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Memorial University of Newfoundland: Digital Archives Initiative (DAI) |
op_collection_id |
ftmemorialunivdc |
language |
English |
topic |
CEA (Oncology) Monoclonal antibidies |
spellingShingle |
CEA (Oncology) Monoclonal antibidies Reddy, Vijay Subba, 1961- Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin |
topic_facet |
CEA (Oncology) Monoclonal antibidies |
description |
Thesis (Ph.D.)--Memorial University of Newfoundland, 1993. Medicine Bibliography: leaves 250-275 The objective of this project was to produce bispecific monoclonal antibodies (BsMabs) which recognise both the tumour associated carcinoembryonic antigen (CEA) and the chemotherapeutic agent doxorubicin, as a complementary approach to the use of immunoconjugates for site specific drug delivery. A monoclonal anti-CEA hybridoma (11-285-14) was made sensitive to hypoxanthine, aminopterin and thymidine (HAT) , by back selecting it in increasing concentrations of 8- azaguanine. Eight 8-azaguanine resistant fusion partners were selected based on growth characteristics and continued anti- CEA production. As doxorubicin (Dox) is a hapten, it was conjugated to carrier proteins keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA) using l-ethyl-3- (dimethyl-aminopropyl) carbodiimide. Dox-KLH arid Dox-BSA conjugates were employed to immunize mice and spleen cells were used for fusions with the HAT sensitive anti-CEA 11-285-14 using standard hybridoma procedures. Enzyme linked immunosorbent assays (ELISAs) were developed to test the hybrids obtained for anti-CEA, anti-Dox, anti-BSA and dual bispecific activity. Sixteen fusions from Dox-KLH immunized mice yielded 621 hybrids of which 47 showed low level bispecificity. Eight fusions with Dox-BSA immunized mice yielded 297 hybrids. Hybrids showing dual activities were cloned and 7 out of 286 of the positive clones have been selected for expansion. |
author2 |
Memorial University of Newfoundland. Faculty of Medicine |
format |
Thesis |
author |
Reddy, Vijay Subba, 1961- |
author_facet |
Reddy, Vijay Subba, 1961- |
author_sort |
Reddy, Vijay Subba, 1961- |
title |
Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin |
title_short |
Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin |
title_full |
Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin |
title_fullStr |
Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin |
title_full_unstemmed |
Production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (CEA) and doxorubicin |
title_sort |
production of bispecific monoclonal antibodies recognising both carcinoembryonic antigen (cea) and doxorubicin |
publishDate |
1993 |
url |
http://collections.mun.ca/cdm/ref/collection/theses3/id/80389 |
long_lat |
ENVELOPE(-67.338,-67.338,-68.785,-68.785) |
geographic |
Keyhole |
geographic_facet |
Keyhole |
genre |
Newfoundland studies University of Newfoundland |
genre_facet |
Newfoundland studies University of Newfoundland |
op_source |
Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries |
op_relation |
Electronic Theses and Dissertations (32.18 MB) -- http://collections.mun.ca/PDFs/theses/Reddy_VijaySubba.pdf 76165746 http://collections.mun.ca/cdm/ref/collection/theses3/id/80389 |
op_rights |
The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. |
_version_ |
1766113107483033600 |