Journal Article

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

Gartner, Jared, Feldman, Steven A., Zacharakis, Nikolaos, Chinnasamy, Harshini, Lu, Yong-Chen, Black, Mary, Trebska-McGowan, Katarzyna, Prickett, Todd, Langhan, Michelle, Xu, Hui, Rosenberg, Steven A., Pasetto, Anna, Shelton, Thomas, Robbins, Paul F., Goff, Stephanie L., Jia, Li, Somerville, Robert P., Zheng, Zhili

2018

Overview

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. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/251 / 631/67/1059/2325 / 692/308/575 / 692/699/67 / 692/699/67/1347 / Adoptive Transfer / Anticancer properties / Antitumor activity / B cells / Bile ducts / Biomedical and Life Sciences / Biomedicine / Bladder / Bladder cancer / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - immunology / Cancer / Cancer metastasis / Cancer Research / Cancer treatment / Care and treatment / Cervix / Coding / Colon / Elderly women / Female / Fusion Regulatory Protein 1, Heavy Chain - genetics / Gastrointestinal system / Gastrointestinal tract / Gene mutation / Genes / Genetic aspects / Health aspects / Humans / Immune checkpoint / Immunotherapy / Infectious Diseases / Interleukins / Letter / Lung cancer / Lymphocytes / Lymphocytes, Tumor-Infiltrating - immunology / Medical schools / Melanoma / Metabolic Diseases / Metastases / Metastasis / Middle Aged / Molecular Medicine / Mutation / Mutation - genetics / Mutation rates / Neoplasm Metastasis / Neurosciences / Patients / Proteasome Endopeptidase Complex - genetics / Proteins / Remission Induction / Smoking / T cells / Tumor-infiltrating lymphocytes / Tumors