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

Immune recognition of somatic mutations leading to complete durable regression in metastatic... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Medicine Springer Journals

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Publisher
Springer Journals
Copyright
Copyright © 2018 by The Author(s)
Subject
Biomedicine; Biomedicine, general; Cancer Research; Metabolic Diseases; Infectious Diseases; Molecular Medicine; Neurosciences
ISSN
1078-8956
eISSN
1546-170X
D.O.I.
10.1038/s41591-018-0040-8
Publisher site
See Article on Publisher Site

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 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.

Journal

Nature MedicineSpringer Journals

Published: Jun 4, 2018

References

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