Dendritic cells pulsed with an anti-idiotype antibody mimicking Her-2/neu induced protective antitumor immunity in two lines of Her-2/neu transgenic mice.
Her-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. To test the efficacy of immune-based strategies in eliciting an antitumor response, we have evaluated the vaccine potential of an anti-idiotype (Id) antibody, 6D12 in tolerant hosts. Immunization of human Her-2/neu transgenic mice with 6D12-pulsed dendritic cells (DC) could reverse Her-2/neu unresponsiveness and result in the induction of Her-2/neu-specific humoral and cellular immune responses and protection against tumors expressing Her-2/neu. Furthermore, the tumor rejection in 6D12-pulsed DC immunized mice was associated with development of memory response. Vaccination of transgenic female FVB-neuN mice that carry the rat Her-2/neu oncogene, markedly delayed tumor onset and developed significantly fewer spontaneous mammary tumors compared with mice treated with control vaccine. Tumor growth inhibition was associated with the induction of Her-2/neu-specific immune responses. These data suggest the potential use of anti-Id antibody 6D12 as a vaccine for immunotherapy of Her-2/neu-positive human cancer.
Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. asaha@umn.edu
Asim
A
Saha
Sunil K
SK
Chatterjee
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism*; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D009368:Neoplasm Transplantation; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human; C508053:ERBB2 protein, human