Idiotype-Based Immunotherapy of Cancers

Abstract

Idiotypes are sets of antigenic determinants (idiotopes) expressed by variable (V) regions of immunoglobulin molecules (Kunkel et al. 1963; Oudin and Michel 1963). The terminology often extends to antigenic determinants of V regions of T cell receptors. Thus, each antibody molecule, B cell clone, and T cell clone possess unique idiotypes that characterize the structural diversity of V regions of T and B cell clones. Idiotopes are defined serologically by their complementary anti-idiotypic antibodies. Thus, idiotypes, per se, are not physicochemical entities, even though they have a structural basis that is largely or entirely within the hypervariable regions or complementarity-determining regions (CDRs) of the immunoglobulin variable domain. The hypervariable sequences that provide the structural basis for idiotypic determinants reflect inherited germline diversity in the case of natural, unmutated antibodies, and somatic mutations of V genes in the case of antigen-driven antibody responses. An idiotype that is encoded by germ line V genes may be shared by several antibody molecules that recognize an antigen (cross-reactive idiotype, CRI), whereas idiotopes that arise from somatic events define the products of only one or a few clones of antibody-producing B cells (private idiotype) (Kohler et al. 1988).