Generation of Her-2/neu vaccine utilizing idiotypic network cascade.
Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or overexpression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. Our strategy is active specific immunotherapy in which patients immunized with an anti- Id antibody mimicking Her-2/neu will generate sustained high titer Her-2/neu specific protective antibodies. We have used an anti-Her-2/neu murine monoclonal antibody 4D5 as the immunizing antibody (Ab1) against which monoclonal anti-Ids or Ab2s were generated in syngeneic mice. We have characterized one such anti-Id (Ab2) designated 6D12, which mimics a specific epitope of Her-2/neu as defined by Trastuzumab, and can be used as a surrogate antigen for Her-2/neu across the species barriers. Immunization of allogeneic mice or rabbits with 6D12 induced anti-anti-Id (Ab3), that specifically recognized Her-2/neu-positive tumor cells and lysed these cells in culture by antibody-dependent cellular cytotoxicity (ADCC). Monoclonal Ab3 generated in mice against 6D12 inhibited the proliferation of Her-2/neu-positive SK-BR-3 cells in vitro in a dose dependent fashion and delayed the growth of Her-2/neu transfected EL4-Her-2 cells in vivo. These data suggest the potential use of 6D12 as a vaccine for Her-2/neu-positive human cancer.
Pal
Smarajit
S
Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
Saha
Asim
A
Mohanty
Kartik
K
Mallick
Palash
P
Chatterjee
Sunil K
SK
Foon
Kenneth A
KA
Bhattacharya-Chatterjee
Malaya
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002455:Cell Division; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D000090063:Proto-Oncogene Mas; D011817:Rabbits; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human; C508053:ERBB2 protein, human