Fast-tracked CTL: Rapid induction of potent anti-tumor killer T cells in situ

Karin L. Heckman, Erin L. Schenk, Suresh Radhakrishnan, Kevin D. Pavelko, Michael J. Hansen, Larry R. Pease

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Current strategies to elicit cytolytic T cell responses specific for tumor-associated or over-expressed self antigens rely on multiple immunizations and in vitro expansion schemes. Here we report the in vivo induction of activated tumor-specific CD8+ CTL just 6 days after treatment with the IgM immune modulator B7-DC XAb. Antibody treatment of mice at the time of tumor challenge elicited potent CTL with a specificity that distinguished between MHC-compatible tumors. Remarkably, these effector cells were not generated by the extensive proliferation of naive CTL precursors, though their induction required CD4+ T cell help and classical B7 costimulatory signals. Tumor targets were recognized and lysed in an MHC-restricted, perforin-dependent manner, indicating that these rapidly induced effectors resemble traditionally defined CTL, despite the finding that strong increases in the expression of the effector/memory marker CD44 and the activation marker CD69 were not elicited. These CTL were induced in animals bearing well-established tumors and resulted in anti-tumor protection, underscoring the therapeutic potential of this type of effector T cell population in cancer patients.

Original languageEnglish (US)
Pages (from-to)1827-1835
Number of pages9
JournalEuropean Journal of Immunology
Volume37
Issue number7
DOIs
StatePublished - Jul 1 2007

Keywords

  • Costimulatory molecules
  • Cytotoxicity
  • Dendritic cells
  • T cells
  • Tumor immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Heckman, K. L., Schenk, E. L., Radhakrishnan, S., Pavelko, K. D., Hansen, M. J., & Pease, L. R. (2007). Fast-tracked CTL: Rapid induction of potent anti-tumor killer T cells in situ. European Journal of Immunology, 37(7), 1827-1835. https://doi.org/10.1002/eji.200637002