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.
Institute for Systems Biology
Peng, Songming; Zaretsky, Jesse M; Ng, Alphonsus H C; Chour, William; Bethune, Michael T; Choi, Jongchan; Hsu, Alice; Holman, Elizabeth; Ding, Xiaozhe; Guo, Katherine; Kim, Jungwoo; Xu, Alexander M; Heath, John E; Noh, Won Jun; Zhou, Jing; Su, Yapeng; Lu, Yue; McLaughlin, Jami; Cheng, Donghui; Witte, Owen N; Baltimore, David; Ribas, Antoni; and Heath, James R, "Sensitive Detection and Analysis of Neoantigen-Specific T Cell Populations from Tumors and Blood." (2019). Articles, Abstracts, and Reports. 2185.