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

Carmen P. Wong, Craig Y. Okada, Ronald Levy

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Tumor-specific TCR can serve as an effective target for active immunotherapy of T cell malignancies. Using the murine T cell tumor model C6VL, vaccination with C6VL TCR protected mice from a subsequent lethal dose of tumor cells. This study characterizes the immune mechanisms involved in the tumor protection, and the influence of immunologic adjuvants in inducing a protective immune response. Immune responses induced by TCR vaccines formulated with 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-type, reflected by the induction of IgG2a and IgG2b anti-C6VL TCR Abs. CD40L and GM-CSF exclusively produced IgG1 Abs, reflecting a Th2-type immune response. In our tumor model system, only vaccines containing adjuvants that induced a Th1-type immune response favored tumor protection. Furthermore, we demonstrated that CD8+ T cells were necessary and sufficient for tumor protection using anti-CD8 mAb depletion and adoptive cell transfer experiments. Transfer of hyperimmune serum containing anti-C6VL TCR Abs into naive mice had modest anti-tumor effects and was not sufficient to prevent tumor growth. TCR-vaccinated B cell-deficient mice were not protected against C6VL tumor, and tumor protection was not completely restored after hyperimmune serum transfer. Thus, B cells may serve as important APCs in inducing a protective immune response. Based on these results future TCR vaccines should be designed to maintain native TCR conformation, as well as induce a strong Th1-type immune response.

Original languageEnglish (US)
Pages (from-to)2251-2258
Number of pages8
JournalJournal of Immunology
Volume162
Issue number4
StatePublished - Feb 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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