B-cell lymphomas are monoclonal tumor cell populations which arise by proliferation of a single neoplastic B lymphocyte. The immunoglobulins expressed by these tumor cells have idiotype determinants which are tumor specific antigens. Antibodies against these unique antigenic determinants (anti-idiotype antibodies) are exceedingly useful reagents for monitoring tumor load, for diagnosis and possible therapy of B-cell malignancies. However, current methodology for the production of anti-idiotype antibodies against human B-cell lymphomas is labor intensive and not readily applicable to all B-cell lymphomas. We propose to develop a new methodology for the production of anti-idiotype antibodies against B-cell lymphomas. Recent advances in molecular biology provide techniques for the rapid cloning and sequencing of the genes which encode the immunoglobulin variable region in a B-cell lymphoma. The protein sequence of the variable region can be deduced from the DNA sequence, and peptides homologous to specific portions of the variable region (CDR segments) can be synthesized. These synthetic peptides can be used to elicit anti-idiotype antibodies specific for the B-cell lymphoma. The feasibility of using synthetic peptides to elicit tumor specific immunity will be tested initially with a murine B-cell leukemia (BCL). We will assess the ability of synthetic peptides to induce anti-idiotype humoral responses, cytolytic T-cell responses, and active in vivo immunity in tumor-bearing mice. By using an animal model system, we can perform carefully controlled experiments to assess the efficacy of synthetic peptides for eliciting tumor-specific immunity. We will also clone and sequence the expressed variable region genes from two human B-cell lymphomas. Peptides homologous to CDR segments of these V regions will be synthesized and will be tested as immunogens for the production of tumor-specific, anti-idiotype antibodies in rabbits and mice. (HI)
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