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

Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.

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.

Trial registration: ClinicalTrials.gov NCT01174121.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adoptive Transfer / methods*
  • Adult
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / therapy*
  • Bile Ducts, Intrahepatic*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / therapy*
  • Clinical Trials, Phase II as Topic
  • Exome
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / transplantation*
  • Mutation
  • Receptor, ErbB-2 / metabolism
  • Th1 Cells / transplantation*

Substances

  • Adaptor Proteins, Signal Transducing
  • ERBIN protein, human
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT01174121