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

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.
Authors	Nikolaos Zacharakis, Harshini Chinnasamy, Mary Black, Hui Xu, Yong-Chen Lu, Zhili Zheng, Anna Pasetto, Michelle Langhan, Thomas Shelton, Todd Prickett, Jared Gartner, Li Jia, Katarzyna Trebska-McGowan, Robert P Somerville, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman
Journal	Nature medicine (Nat Med) Vol. 24 Issue 6 Pg. 724-730 (06 2018) ISSN: 1546-170X [Electronic] United States
PMID	29867227 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	ECPAS protein, human Fusion Regulatory Protein 1, Heavy Chain SLC3A2 protein, human Proteasome Endopeptidase Complex
Topics	Adoptive Transfer Breast Neoplasms (genetics, 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

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