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

E Tran, S Turcotte, A Gros, PF Robbins, YC Lu… - Science, 2014 - science.org
E Tran, S Turcotte, A Gros, PF Robbins, YC Lu, ME Dudley, JR Wunderlich, RP Somerville…
Science, 2014science.org
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 …
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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