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

• Published in: The Journal of immunology (1950) Vol. 172; no. 2; pp. 929 - 936
• Main Authors: Lambert, Stacie L, Okada, Craig Y, Levy, Ronald
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.2004
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antibodies, Neoplasm - biosynthesis; Antibodies, Neoplasm - physiology; Antibody-Dependent Cell Cytotoxicity - genetics; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Line, Tumor; Female; Hemocyanins - administration & dosage; Hemocyanins - immunology; Immunization, Passive; Immunoglobulin G - biosynthesis; Immunoglobulin G - physiology; Immunoglobulin Isotypes - biosynthesis; Immunoglobulin Isotypes - physiology; Interferon-gamma - physiology; Interleukin-12 - administration & dosage; Interleukin-12 - immunology; keyhole limpet hemocyanin; Lymphoma, T-Cell - immunology; Lymphoma, T-Cell - prevention & control; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, T-Cell, alpha-beta - administration & dosage; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Fc - physiology; T cell lymphoma; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.2.929

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 CD8alpha knockout, micro MT, and FcgammaR 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-gamma knockout mice demonstrated a requirement for IFN-gamma, probably via generation of IgG2c Abs, in vaccine-induced tumor protection. IFN-gamma 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.