TCR vaccines for active immunotherapy of T cell malignancies.
We have developed a TCR-based vaccine approach for the treatment of T cell malignancies. TCR genes were isolated from C6VL, a T cell tumor of C57BL/Ka origin. The transmembrane encoding domains of the TCR genes were replaced by sequences encoding for phosphatidylinositol-linked cell surface expression. A high expressing cell line was produced by transfection and amplification of the TCR genes. Large quantities of soluble native C6VL TCR-alphabeta protein was obtained by treating the high-expressing cells with a specific phospholipase and purifying the released TCR by affinity chromatography. Following vaccination with the TCR linked to keyhole limpet hemocyanin, specific anti-TCR humoral responses were induced. Both the carrier protein and an adjuvant were required for optimal responses. Hyperimmune serum from vaccinated mice reacted specifically with C6VL cells, and the immunizations did not affect the TCR repertoire, which suggested that the immune response was Id specific. The TCR-vaccinated mice were specifically protected from a lethal number of C6VL tumor cells. B cell-deficient mice were not protected by TCR vaccinations. Similarly, TCR-immunized mice depleted of CD8+ cells prior to tumor challenge were not protected. Thus, C6VL TCR vaccine effectively stimulated tumor protection, which depends on the presence of both B cells and CD8+ T cells.
Okada
C Y
CY
Stanford University School of Medicine, Department of Medicine, CA 94305, USA. cokada@leland.stanford.edu
Wong
C P
CP
Denney
D W
DW
Levy
R
R
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007114:Immunization; D016399:Lymphoma, T-Cell / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010716:Phosphatidylinositols / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014162:Transfection; D014614:Vaccines, Synthetic
D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D014614:Vaccines, Synthetic