医学
过继性细胞移植
乳腺癌
免疫疗法
免疫检查点
黑色素瘤
免疫学
癌症
癌症研究
转移性乳腺癌
肿瘤科
内科学
免疫系统
T细胞
作者
Nikolaos Zacharakis,Harshini Chinnasamy,Mary A. Black,Hui Xu,Yong Lu,Zhili Zheng,Anna Pasetto,Michelle M. Langhan,Thomas E. Shelton,Todd D. Prickett,Jared J. Gartner,Jia Li,Katarzyna Trebska-McGowan,Robert Somerville,Paul F. Robbins,Steven A. Rosenberg,Stephanie L. Goff,Steven A. Feldman
出处
期刊:Nature Medicine
[Springer Nature]
日期:2018-06-01
卷期号:24 (6): 724-730
被引量:586
标识
DOI:10.1038/s41591-018-0040-8
摘要
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.
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