Cancer Immunotherapy Based on Mutation-Specific CD4+T Cells in a Patient with Epithelial Cancer

被引：1356

作者：

Tran, Eric ^{[1
]}

Turcotte, Simon ^{[1
]}

Gros, Alena ^{[1
]}

Robbins, Paul F. ^{[1
]}

Lu, Yong-Chen ^{[1
]}

Dudley, Mark E. ^{[1
]}

Wunderlich, John R. ^{[1
]}

Somerville, Robert P. ^{[1
]}

Hogan, Katherine ^{[1
]}

Hinrichs, Christian S. ^{[1
]}

Parkhurst, Maria R. ^{[1
]}

Yang, James C. ^{[1
]}

Rosenberg, Steven A. ^{[1
]}

机构：

[1] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE | 2014年 / 344卷 / 6184期

关键词：

CD4(+) T-CELLS; METASTATIC MELANOMA; ESTABLISHED MELANOMA; TUMOR-REGRESSION; LUNG-CARCINOMA; IFN-GAMMA; IN-VIVO; LYMPHOCYTES; GENE; RESPONSES;

D O I：

10.1126/science.1251102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (T(H)1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional T(H)1 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 T(H)1 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.

引用

页码：641 / 645

页数：5

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