Simultaneous targeting of tumor antigens and the tumor vasculature using t lymphocyte transfer synergize to induce regression of established tumors in mice

Dhanalakshmi Chinnasamy, Eric Tran, Zhiya Yu, Richard A. Morgan, Nicholas P. Restifo, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Most systemic cancer therapies target tumor cells directly, although there is increasing interest in targeting the tumor stroma that can comprise a substantial portion of the tumor mass. We report here a synergy between two T-cell therapies, one directed against the stromal tumor vasculature and the other directed against antigens expressed on the tumor cell. Simultaneous transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the VEGF receptor-2 (VEGFR2; KDR) that is overexpressed on tumor vasculature and T-cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumorfree survival of mice compared with treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion before cell transfer was required to mediate the antitumor effect. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/or persistence of the adoptively transferred tumor antigen-specific T cells in the tumor microenvironment and thus enhanced their antitumor potency. The data presented here emphasize the possible beneficial effects of combining antiangiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer.

Original languageEnglish (US)
Pages (from-to)3371-3380
Number of pages10
JournalCancer Research
Volume73
Issue number11
DOIs
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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