Sensitive Detection and Analysis of Neoantigen-Specific T Cell Populations from Tumors and Blood.
Cell Rep
; 28(10): 2728-2738.e7, 2019 09 03.
Article
in En
| MEDLINE
| ID: mdl-31484081
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Melanoma
/
Antigens, Neoplasm
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2019
Document type:
Article
Affiliation country:
United States