Immunization with anti‐idiotype monoclonal antibodies bearing the internal image of the renal‐cell carcinoma‐associated antigen G250 induces specific cellular immune responses

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Abstract
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 Ab l') 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.