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 ovary 1-7 . 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 cancers 8-11 . 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.
CITATION STYLE
Zacharakis, N., Chinnasamy, H., Black, M., Xu, H., Lu, Y. C., Zheng, Z., … Feldman, S. A. (2018). Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nature Medicine, 24(6), 724–730. https://doi.org/10.1038/s41591-018-0040-8
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