Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer.

Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer.
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DOI:
10.1126/science.1251102
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发表时间:
2014-05-09
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Rosenberg SA
Rosenberg SA
中科院分区:
其他
文献类型:
--
作者:
Tran E;Turcotte S;Gros A;Robbins PF;Lu YC;Dudley ME;Wunderlich JR;Somerville RP;Hogan K;Hinrichs CS;Parkhurst MR;Yang JC;Rosenberg SA

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有限的证据表明,人类对上皮细胞癌症产生突变特异性T细胞反应。我们使用基于全外显子组测序的方法来证明转移性胆管癌患者的肿瘤浸润淋巴细胞(TIL)含有CD4+ T辅助1 (TH1)细胞,可识别肿瘤表达的erbb2相互作用蛋白(ERBB2IP)突变。在过继转移含有约25%突变特异性多功能TH1细胞的TIL后,患者实现了目标病变的减少,并延长了疾病的稳定时间。疾病进展后,患者接受>95%纯突变反应性TH1细胞群治疗,再次经历肿瘤消退。这些结果提供了证据,证明CD4+ T细胞对突变抗原的反应可以被利用来介导转移性上皮癌的消退。
Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (TH1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional TH1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. Upon disease progression, the patient was retreated with a >95% pure population of mutation-reactive TH1 cells and again experienced tumor regression. These results provide evidence that a CD4+ T cell response against a mutated antigen can be harnessed to mediate regression of a metastatic epithelial cancer.
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