Sensitive Detection and Analysis of Neoantigen-Specific T Cell Populations from Tumors and Blood.
Antigens, Neoplasm
/ blood
Biopsy
HEK293 Cells
Humans
Immunotherapy
Jurkat Cells
Kinetics
Lymphocytes, Tumor-Infiltrating
/ immunology
Magnetite Nanoparticles
/ chemistry
Major Histocompatibility Complex
Melanoma
/ blood
Nucleic Acids
/ metabolism
Programmed Cell Death 1 Receptor
/ immunology
Receptors, Antigen, T-Cell
/ metabolism
Reproducibility of Results
T-Lymphocytes
/ immunology
Tomography, X-Ray Computed
T cell receptor
cancer immunotherapy
microfluidics
nanotechnology
neoantigens
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
03 09 2019
03 09 2019
Historique:
received:
04
07
2017
revised:
04
05
2019
accepted:
29
07
2019
entrez:
5
9
2019
pubmed:
5
9
2019
medline:
15
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31484081
pii: S2211-1247(19)31022-8
doi: 10.1016/j.celrep.2019.07.106
pmc: PMC6774618
mid: NIHMS1051674
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Magnetite Nanoparticles
0
Nucleic Acids
0
Programmed Cell Death 1 Receptor
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2728-2738.e7Subventions
Organisme : NCI NIH HHS
ID : F32 CA213966
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA170689
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197633
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA199090
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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