Immunization with anti-idiotype monoclonal antibodies bearing the internal image of the renal-cell carcinoma-associated antigen G250 induces specific cellular immune responses.
We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor-associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called AbI') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell-mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DTH responses, whereas no significant DTH response was observed with G250-negative cells. This antigen-specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2-sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor-specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients.
Uemura
H
H
Department of Urology, University Hospital Nijmegen, The Netherlands.
Okajima
E
E
Debruyne
F M
FM
Oosterwijk
E
E
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology*; D051379:Mice; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm