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

By Nikolaos Zacharakis, Harshini Chinnasamy, Mary A. Black, Hui Xu, Yong-Chen Lu, Zhili Zheng, A. Pasetto, Michelle M. Langhan, Thomas E. Shelton, Todd D Prickett and 8 more. Nature Medicine, 2018

708 citations recorded by the source corpus.

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. Adoptive T cell therapy induced complete and durable remission in a patient with refractory metastatic breast cancer, providing proof of principle for this approach in breast cancer therapy.

Subfields: Cancer Research, Oncology

View Paper: https://www.semanticscholar.org/paper/6914cba9f35cd76dc4233372f72bdfe7b3d79f5f

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Citations in the corpus

• Neoantigens: promising targets for cancer therapy (2023, background): “5 years after therapy.(377) Patients with metastatic melanoma who are resistant to current therapies might achieve objective response rates of 50% to 70% with autologous TIL transfer and IL-2 after host lymphodepletion by total-body irradiation or chemotherapy.”