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

TLDR

Evidence that humans can mount mutation‑specific T cell responses to epithelial cancers is limited. Whole‑exome sequencing revealed that tumor‑infiltrating CD4+ T helper 1 cells in a metastatic cholangiocarcinoma patient recognized a mutation in ERBB2IP. Adoptive transfer of mutation‑specific CD4+ T helper 1 cells led to lesion reduction and disease stabilization, and retreatment with a highly pure population induced further regression, demonstrating that CD4+ T cell responses to mutated antigens can drive regression of metastatic epithelial cancer.

Abstract

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.