Anti-idiotype cancer vaccines: past and future

Abstract

Anti-idiotypic antibodies (Ab2) binding to the antigen-combining site of antitumor antibodies (Ab1) can induce anti-anti-idiotypic antibodies (Ab3) that specifically bind to the tumor antigen recognized by Ab1. Furthermore, Ab2, mimicking tumor antigens, have been shown to induce anti-anti-idiotypic proliferative T lymphocytes of the helper and suppressor type, as well as cytotoxic lymphocytes. The immunomodulatory activities of Ab2 have been demonstrated both in animals and in patients. The demonstration of tumor growth inhibition by anti-idiotypes in preclinical and phase I clinical studies emphasizes that randomized control trials should be performed to demonstrate clinical efficacy of Ab2 vaccines.

Induction of Human Anti-Human Antibody Responses (Ab2) after Application of a Humanized Lewis Y Carbohydrate Specific Antibody (Ab1): Connection of Prolonged Disease Stabilization with Ab3 Induction?

“…Whereas the immunological implications of the HAMA response have been investigated in great detail [7][8][9], the potential therapeutic effect of the HAHA response is largely unknown. In this regard the induction of anti-idiotypic network responses may even be involved in mediating effector mechanisms [10][11][12]. These effects can be explained based on the anti-idiotypic network theory postulated by Jerne [13].…”

Examination of a role for idiotypy in the disease remission of a long-term survivor of adult T cell leukemia treated with anti-Tac antibody

“…19 This suggested that antibody immunotherapy may be able to induce T cell responses against an original target antigen. Other protocols immunized actively with preformed Ab2 antibodies of xenogeneic or human origin to the same effect, [47][48][49] inducing Ab3 and T3 by single step responses.…”

Expression of an antigen homologous to the human CO17-1A/GA733 colon cancer antigen in animal tissues

“…However, the relevance of preclinical studies of targeting this antigen in passive and active immunotherapy (with MAbs, anti-idiotypic antibodies, and recombinant antigen; reviewed in Herlyn et al, 1982Herlyn et al, , 1995Herlyn et al, , 1996 for clinical trials in patients has been difficult to determine in the absence of information on normal tissue expression of the antigen homologue in animals. We demonstrate here that an antigen homologous to the human gastrointestinal carcinoma-associated antigen GA733 is expressed by normal intestine and liver of mice, rats and nonhuman primates, as determined by immunohistoperoxidase staining of tissues.…”

“…Previous studies of experimental passive and active immunotherapy targeting the human GA733 antigen in mice (Herlyn et al, 1982(Herlyn et al, , 1997) must be interpreted with caution, keeping in mind the immunological differences between the human antigen and its homologue. Thus, passive immunotherapy with MAb C017-lA and GA733 (Herlyn et al, 1982 and active immunotherapy with anti-idiotypic antibodies mimicking the GA733 or C017-IA epitope or with recombinant GA733 antigen (reviewed in Herlyn et al, , 1996 have been performed in mice which, in contrast to humans, do not express the C017-lA and GA733 epitopes on normal tissues. The differences in the GA733 epitope tissue expression between mice and humans might explain why treatment of mice with MAb GA733 was not accompanied by toxicity , whereas this MAb showed dose-limiting toxicity to gastrointestinal organs in colon cancer patients .…”