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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

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

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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
DOI
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 Medicine – Springer Journals

Published: Jun 4, 2018

References

  • Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer
    Reck, M
  • Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomized dose-comparison cohort of a phase 1 trial
    Robert, C
  • MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
    Powles, T
  • Signatures of mutational processes in human cancer
    Alexandrov, LB
  • Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer
    Dawood, S
  • Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
    Le, DT
  • Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer
    Hamanishi, J
  • Immunogenicity of somatic mutations in human gastrointestinal cancers
    Tran, E
  • T cell transfer therapy targeting mutant KRAS in cancer
    Tran, E
  • Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer
    Tran, E
  • Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer
    Stevanović, S
  • The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data
    Cerami, E
  • Mutational profile of metastatic breast cancers: a retrospective analysis
    Lefebvre, C
  • Comprehensive molecular portraits of human breast tumors
  • Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens
    Dudley, ME
  • Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes
    Abate-Daga, D
  • Characterization of an immunogenic mutation in a patient with metastatic triple-negative breast cancer
    Assadipour, Y
  • Simplified method of the growth of human tumor-infiltrating lymphocytes (TIL) in gas-permeable flasks to numbers needed for patient treatment
    Jin, J
  • Tumor- and neoantigen-reactive T cell receptors can be identified based on their frequency in fresh tumor
    Pasetto, A
  • Enhanced antitumor activity of murine–human hybrid T cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR–CD3 stability
    Cohen, CJ; Zhao, Y; Zheng, Z; Rosenberg, SA; Morgan, RA
  • Incorporation of transmembrane hydrophobic mutations in the TCR enhance its surface expression and T cell functional avidity
    Haga-Friedman, A; Horovitz-Fried, M; Cohen, CJ
  • Fisher and the making of maximum likelihood. 1912–1922
    Aldrich, JRA