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Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
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Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
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Journal Article
Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
2014
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
Adaptor Proteins, Signal Transducing - genetics
/ Adult
/ Bile Duct Neoplasms - genetics
/ Bile Duct Neoplasms - therapy
/ Cancer
/ CD4-Positive T-Lymphocytes - immunology
/ Cells
/ Cholangiocarcinoma - genetics
/ Cholangiocarcinoma - therapy
/ Clinical Trials, Phase II as Topic
/ Exome
/ Female
/ Humans
/ Lymphocytes, Tumor-Infiltrating - transplantation
/ Mutation
/ Patients
/ Receptor, ErbB-2 - metabolism
/ Tumors
