Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer

Nat Med. 2018 Jun;24(6):724-730. doi: 10.1038/s41591-018-0040-8. Epub 2018 Jun 4.

Abstract

Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary1-7. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers8-11. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology*
  • Female
  • Fusion Regulatory Protein 1, Heavy Chain / genetics
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Metastasis
  • Proteasome Endopeptidase Complex / genetics
  • Remission Induction

Substances

  • ECPAS protein, human
  • Fusion Regulatory Protein 1, Heavy Chain
  • SLC3A2 protein, human
  • Proteasome Endopeptidase Complex