Anti-idiotypic antibodies and the induction of specific tumor immunity

Immunization with anti-idiotypic antibodies is a strategy which, with variable success, can be used to elicit or amplify antigen-specific immune response. This article discusses the manipulation of specific idiotypes in anti-tumor immunity, emphasizing the appropriate consideration of genetic restriction, the choice of idiotype specificity, and the route of immunization. Two independent pathways are outlined: One uses anti-idiotypic antibodies to select and amplify tumor-specific T and B cells via their preexisting antigen-specific receptors, and the other uses anti-idiotypes as primary internal image immunogens to elicit immune recognition of determinants shared by the anti-idiotype and by tumor-associated antigens. Both pathways can be manipulated in attempts to favor the generation of anti-tumor effector cells and minimize the elicitation of suppression. Anti-idiotypic immunization can be utilized to induce therapeutic immune reactivity in hosts lacking effective direct anti-tumor responses. By stimulating ‘silent’, or normally suppressed, T and B cell clones, appropriate immunization strategies can circumvent immune regulatory pathways associated with suppressor cells and factors derived from such cells. In these studies, adequate characterization of antitumor idiotype and anti-idiotype specificities is key to the experimental approach to tumor therapy using antibodies. The importance of individual host genetic variation in the specificity and scope of immune response to anti-idiotypic immunoglobulins is unknown, and remains an important potential barrier to therapeutic management.