期刊
CELL REPORTS
卷 28, 期 10, 页码 2728-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.07.106
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类别
资金
- Stand Up to Cancer Foundation
- Cancer Research Institute
- National Cancer Institute [1U54 CA199090, R01-CA170689, R35 CA197633]
- Jean Perkins Foundation
- Caltech
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
- Banting Postdoctoral Fellowship from the Government of Canada
- Ruth L. Kirschstein F32 Postdoctoral Fellowship from the National Cancer Institute [1F32CA213966-01]
Neoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging. Here, we describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex (MHC) tetramers at high avidity by barcoded DNA linkers. The magnetic particles provide a convenient handle to isolate the desired cell populations, and the barcoded DNA enables multiplexed analysis. The method exhibits superior recovery of antigen-specific T cell populations relative to literature approaches. We applied the method to profile neoantigen-specific T cell populations in the tumor and blood of patients with metastatic melanoma over the course of anti-PD1 checkpoint inhibitor therapy. We show that the method has value for monitoring clinical responses to cancer immunotherapy and might help guide the development of personalized mutational neoantigen-specific T cell therapies and cancer vaccines.
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