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TCR Vaccines against a Murine T Cell Lymphoma: A Primary Role for Antibodies of the IgG2c Class in Tumor Protection¹

Stacie L. Lambert^*, Craig Y. Okada and Ronald Levy^2,*

^* Division of Oncology and Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305; and Division of Hematology and Oncology, Research Service, Veterans Affairs Medical Center and University of Michigan, Ann Arbor, MI 48105

Tumor-associated proteins can act as effective immunotherapeutic targets. Immunization with tumor TCR protein conjugated to the immunogenic protein keyhole limpet hemocyanin (KLH) protects mice from tumor challenge with the murine T cell lymphoma C6VL. The immune mechanisms responsible for this tumor protection are of interest for designing more effective vaccine strategies. Previous studies using depletion experiments had suggested a CD8-mediated component of protection induced by TCR-KLH vaccines. In this study we used CD8 knockout, µMT, and FcR knockout mice to investigate the relative roles of CD8⁺ T cells and Ab in protective immunity induced by TCR-KLH immunization. We found that CD8⁺ T cells are not required for tumor protection, although they may contribute to protection. Vaccine-induced Abs are sufficient to mediate protection against this murine T cell lymphoma through an FcR-dependent mechanism. This was confirmed with Ab transfers, which protect challenged mice. Additionally, recombinase-activating gene 1^-/- splenocytes can mediate Ab-dependent cellular cytotoxicity against this tumor in the presence of bound anti-TCR Abs. IFN- knockout mice demonstrated a requirement for IFN-, probably via generation of IgG2c Abs, in vaccine-induced tumor protection. IFN- knockout mice were not protected by immunization and had a severe impairment in IgG2c Ab production in response to immunization. Although mock-depleted anti-TCR Abs could transfer tumor protection, IgG2c-deficient anti-TCR Abs were unable to transfer tumor protection to wild-type mice. These results suggest that TCR-KLH vaccine-induced tumor protection in the C6VL system is primarily attributable to the induction of IgG2c Abs and humoral immunity.

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