TCR Vaccines for Active Immunotherapy of T Cell Malignancies

Craig Okada, Carmen P. Wong, Dan W. Denney, Ronald Levy

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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-αβ 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.

Original languageEnglish (US)
Pages (from-to)5516-5527
Number of pages12
JournalJournal of Immunology
Volume159
Issue number11
StatePublished - Dec 1 1997
Externally publishedYes

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Active Immunotherapy
Vaccines
T-Lymphocytes
Neoplasms
Vaccination
B-Lymphocytes
Phospholipases
Gene Amplification
Phosphatidylinositols
Affinity Chromatography
Genes
Transfection
Immunization
Carrier Proteins
Cell Line
Serum
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Okada, C., Wong, C. P., Denney, D. W., & Levy, R. (1997). TCR Vaccines for Active Immunotherapy of T Cell Malignancies. Journal of Immunology, 159(11), 5516-5527.

TCR Vaccines for Active Immunotherapy of T Cell Malignancies. / Okada, Craig; Wong, Carmen P.; Denney, Dan W.; Levy, Ronald.

In: Journal of Immunology, Vol. 159, No. 11, 01.12.1997, p. 5516-5527.

Research output: Contribution to journalArticle

Okada, C, Wong, CP, Denney, DW & Levy, R 1997, 'TCR Vaccines for Active Immunotherapy of T Cell Malignancies', Journal of Immunology, vol. 159, no. 11, pp. 5516-5527.
Okada C, Wong CP, Denney DW, Levy R. TCR Vaccines for Active Immunotherapy of T Cell Malignancies. Journal of Immunology. 1997 Dec 1;159(11):5516-5527.
Okada, Craig ; Wong, Carmen P. ; Denney, Dan W. ; Levy, Ronald. / TCR Vaccines for Active Immunotherapy of T Cell Malignancies. In: Journal of Immunology. 1997 ; Vol. 159, No. 11. pp. 5516-5527.
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