MONOCLONAL ANTIIDIOTYPIC ANTIBODY FUNCTIONALLY MIMICS THE HUMAN GASTROINTESTINAL CARCINOMA EPITOPE GA733

Anti-idiotypic antibodies (Ab2) that bind to the antigen-combining reg ion of anti-rumor antibodies (Ab1) may functionally, and even structur ally, mimic tumor antigen. We have previously demonstrated that polycl onal goat Ab2 directed against anti-human gastrointestinal carcinoma A b1 GA733 induces anti-anti-idiotypic antibodies (Ab3) in animals that are Ab1-like in their binding specificity and idiotope expression. To obtain more defined Ab2 vaccines with potentially increased specificit y and efficacy, a monoclonal Ab2 (FG1)was produced against Ab1 GA733 i n rats. The monoclonal Ab2 FG1, similar to the polyclonal Ab2 describe d previously, induced Ab3 in rabbits that were Abl-like in their idiot ope expression and binding specificity to tumor cells and antigen. Ant igen-specific Ab3 induced by Ab2 FG I were easily detected in unproces sed rabbit sera, whereas the demonstration of such Ab3 after polyclona l Ab2 immunization required purification of the Ab3 from the rabbit se ra. In addition, Ab2 FGI induced antigen-specific humoral and cellular immunity in mice. Murine Ab3 bound specifically to antigen-positive t umor cells. Ab2-immunized mice showed antigen-specific delayed-type hy persensitivity (DTH) reaction, and cultured splenocytes from the immun e mice demonstrated specific proliferation and cytokine (interferon-ga mma and interleukin-4) secretion upon stimulation with GA733 antigen. However, immune mice were not protected against a challenge with synge neic GA733 antigen-expressing colon carcinoma cells. (C) 1996 Wiley-Li ss, Inc.