T cell antigen receptor vaccines for active immunotherapy of T cell malignancies

We have developed a T cell antigen receptor (TCR) based vaccine for the treatment of T cell malignancies. The murine T cell tumor C6VL was used in this approach. Idiotype TCR vaccines stimulated tumor specific immune responses which specifically protected mice from a subsequent injection of tumor cells. C6VL TCR vaccines made with different adjuvants were compared for their ability to stimulate a humoral and tumor protective immune response. SAF-0, QS-21, IL-12, CD40L, GM-CSF and GM-CSF encapsulated in microspheres were all effective in stimulating a humoral anti-C6VL TCR immune response. Only the immune response stimulated with SAF-1, QS-21, and IL-12 adjuvants protected mice from C6VL tumor challenge. The mechanisms of tumor protection were studied in vivo. The protection stimulated by TCR in SAF-1 required both B cells and CD8+ T cells. TCR vaccines in QS-21, however, do not rely on an intact humoral effector mechanism for their protective effect. Depletion of CD8+ T cells in C6VL TCR QS-21 vaccinated mice negated the protective immune response. Protection mechanism studies using IL-12 as adjuvant is currently underway. To eliminate the need for TCR protein, we have made a recombinant adenovirus encoding for C6VL TCR. Direct inoculation of the virus was not effective in stimulating an anti-C6VL TCR humoral or protective immune response. Currently we are investigating whether dendritic cells infected with C6VL TCR recombinant adenovirus can stimulate a protective immune response.