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 ovary1,2,3,4,5,6,7. 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 cancers8,9,10,11. 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.
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The authors would like to thank A. Mixon and S. Farid of the Surgery Branch FACS Core for assistance with data acquisition and cell sorting, and J. Yang and E. Tran for their valuable discussions. This work was supported by the Center for Cancer Research at the National Cancer Institute (NCI) at the US National Institutes of Health (NIH).
The authors declare no competing interests.
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Zacharakis, N., Chinnasamy, H., Black, M. et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med 24, 724–730 (2018). https://doi.org/10.1038/s41591-018-0040-8
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