Trioma-based vaccination against B-cell lymphoma confers long-lasting tumor immunity.

Abstract

A major goal of tumor immunotherapy is the induction of a systemic immune response against tumor antigens such as the tumor-specific immunoglobulin idiotype (Id) expressed by lymphomas of the B-cell lineage. We describe an approach based on specific redirection of the tumor Id toward professional antigen-presenting cells (APCs), thereby overcoming the inefficient presentation on the parental transformed B cell. Lymphoma cells are fused to a xenogeneic hybridoma cell line that secretes an antibody against a surface molecule on APCs. Due to preferential assembly between heavy and light chains of antibodies of different species-origin, the resulting "trioma" cells produce at high yield a bispecific antibody containing the lymphoma Id and the APC-binding arm, which redirects the Id to APCs. Processing and presentation of the Id will lead to T-cell activation. An absolute requirement for inducing a complete tumor protection was the immunization with antibody-secreting trioma cells as a cell-based vaccine instead of the soluble bispecific antibody. Tumor immunity was specific and long-lasting. Both CD4+ and CD8+ T cells were necessary for inducing tumor immunity.