Cancer patients are usually tolerant to the antigens expressed on tumor cells. Triggering an active immune response by the patients to tumor-associated antigens represents one of the most promising prospects in cancer therapy. In this project, the investigators propose a preclinical study of the anti-idiotype approach to trigger an active immune response against CEA. Certain anti-idiotypic antibodies directed against the variable regions of antibodies specific for a given antigen can mimic (i.e., bear the internal image of) this antigen. In several experimental systems, immunization with anti-idiotypic antibodies elicited specific immunity in lieu of the original antigen. Immunization with anti- idiotype antibodies as surrogate antigens is a promising approach to trigger immunity to tolerized antigens such as tumor antigens. They have already generated baboon polyclonal and rat monoclonal anti-idiotype antibodies that antigenically mimic CEA. In this project they will assess whether these anti-idiotype antibodies can function as surrogate antigens in hamsters. Hamsters have been chosen since they are the only known non-immunodeficient animal species in which human CEA-producing tumors may grow. Hamsters represent a unique model to test whether active anti-idiotype immunization can protect against tumor growth. This Phase I study will represent the basis for more extensive preclinical and clinical studies in Phase II.
