title: Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice.
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 tumor-free 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.
authors: Surgery Branch, National Cancer Institute, Clinical Research Center, Bethesda, MD 20892, USA.
authors: Dhanalakshmi
authors: D
authors: Chinnasamy
authors: Eric
authors: E
authors: Tran
authors: Zhiya
authors: Z
authors: Yu
authors: Richard A
authors: RA
authors: Morgan
authors: Nicholas P
authors: NP
authors: Restifo
authors: Steven A
authors: SA
authors: Rosenberg
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D004195:Disease Models, Animal; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2
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