Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice.
Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice.
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DOI：
10.1158/0008-5472.can-12-3913
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发表时间：
2013-06-01
期刊：
影响因子：
11.2
通讯作者：
Rosenberg SA
中科院分区：
文献类型：
--
作者：
Chinnasamy D;Tran E;Yu Z;Morgan RA;Restifo NP;Rosenberg SA
大多数系统性癌症疗法直接靶向肿瘤细胞，尽管人们对靶向肿瘤基质（可能构成肿瘤块的很大一部分）的兴趣越来越大。我们在这里报告了两种T细胞疗法之间的协同作用，一种针对基质肿瘤血管系统，另一种针对肿瘤细胞上表达的抗原。表达靶向血管内皮生长因子受体-2的嵌合抗原受体的基因工程同基因T细胞的同时转移（VEGFR-2; KDR），其在肿瘤脉管系统和对肿瘤抗原gp 100（PMEL），TRP-1（TYRP 1），或TRP-2（DCT）协同根除小鼠中已建立的B16黑色素瘤肿瘤，并显著增加肿瘤-与用单独的细胞类型或共表达这两种靶向分子的T细胞治疗相比，小鼠的自由存活率。在细胞转移之前需要宿主淋巴细胞清除以介导抗肿瘤作用。协同抗肿瘤反应伴随着肿瘤微环境中过继转移的肿瘤抗原特异性T细胞的浸润和扩增和/或持久性的显著增加，从而增强了它们的抗肿瘤效力。本文提供的数据强调了将抗血管生成与肿瘤特异性免疫抑制方法结合用于治疗癌症患者的可能有益效果。
Most systemic cancer therapies target tumor cells directly though 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 Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2; KDR) that is over expressed 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 to treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion prior to cell transfer was required to mediate the anti-tumor 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 anti-tumor potency. The data presented here emphasize the possible beneficial effects of combining anti-angiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer.