Targeting of cancer neoantigens with donor-derived T cell receptor repertoires
Targeting of cancer neoantigens with donor-derived T cell receptor repertoires
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DOI：
10.1126/science.aaf2288
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发表时间：
2016-06-10
期刊：
影响因子：
56.9
通讯作者：
Schumacher, Ton N.
中科院分区：
文献类型：
--
作者：
Stronen, Erlend;Toebes, Mireille;Schumacher, Ton N.
越来越多的证据表明，临床上有效的癌症免疫治疗是由T细胞对DNA突变衍生的新抗原的反应性推动的。然而，在预测的大量新抗原中，只有一小部分被自体患者T细胞识别，因此扩大新抗原特异性T细胞反应的策略是有吸引力的。我们发现，健康献血者的原始T细胞库提供了新抗原特异性T细胞的来源，响应来自三名患者的57个预测的人类白细胞抗原(HL A)-A*02：01结合表位中的11个。许多T细胞的反应涉及体内被患者自体肿瘤浸润性淋巴细胞忽视的表位。最后，从供者来源的T细胞识别的T细胞受体重定向的T细胞有效地识别含有相关突变的患者来源的黑色素瘤细胞，为在癌症免疫治疗中使用这种“外包”免疫反应提供了理论基础。
Accumulating evidence suggests that clinically efficacious cancer immunotherapies are driven by T cell reactivity against DNA mutation -derived neoantigens. However, among the large number of predicted neoantigens, only a minority is recognized by autologous patient T cells, and strategies to broaden neoantigen-specific T cell responses are therefore attractive. We found that naive T cell repertoires of healthy blood donors provide a source of neoantigen-specific T cells, responding to 11 of 57 predicted human leukocyte antigen (HLA)-A*02:01-binding epitopes from three patients. Many of the T cell reactivities involved epitopes that in vivo were neglected by patient autologous tumor -infiltrating lymphocytes. Finally, T cells redirected with T cell receptors identified from donor -derived T cells efficiently recognized patient -derived melanoma cells harboring the relevant mutations, providing a rationale for the use of such "outsourced" immune responses in cancer immunotherapy.