TCR vaccines against T cell lymphoma: QS-21 and IL-12 adjuvants induce a protective CD8(+) T cell response

Tumor-specific TCR can serve as an effective target for active immunotherap y of T cell malignancies. Using the murine T cell tumor model C6VL, vaccina tion with C6VL TCR protected mice from a subsequent lethal dose of tumor ce lls, This study characterizes the immune mechanisms involved in the tumor p rotection, and the influence of immunologic adjuvants. in inducing a protec tive immune response. Immune responses induced by TCR vaccines formulated w ith various adjuvants: QS-21, IL-12, SAF-1, CD40L, and GM-CSF were compared . QS-21, IL-12, and SAF-1 biased the humoral immune response toward Th1-typ e, reflected by the induction of IgG2a and IgG2b anti-C6VL TCR Abs, CD40L a nd GM-CSF exclusively produced IgG1 Abs, reflecting a Th2-type immune respo nse. In our tumor model system, only vaccines containing adjuvants that ind uced a Th1-type immune response favored tumor protection. Furthermore,,ve d emonstrated that CD8(+) T cells were necessary and sufficient for tumor pro tection using anti-CDS mAb depletion and adoptive cell transfer experiments . Transfer of hyperimmune serum containing anti-C6VL TCR Abs into naive mic e had modest anti-tumor effects and was not sufficient to prevent tumor gro wth, TCR-vaccinated B cell-deficient mice were not protected against C6VL t umor, and tumor protection was not completely restored after hyperimmune se rum transfer. Thus, B cells may serve as important APCs in inducing a prote ctive immune response. Based on these results future TCR vaccines should be designed to maintain native TCR conformation, as well as induce a strong T h1-type immune response.