Faculty, Staff and Student Publications

Publication Date

7-28-2023

Journal

Science Advances

Abstract

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is promising, with early-phase clinical studies showing encouraging responses. However, the transcriptional signatures that control the fate of CAR-NK cells after infusion and factors that influence tumor control remain poorly understood. We performed single-cell RNA sequencing and mass cytometry to study the heterogeneity of CAR-NK cells and their in vivo evolution after adoptive transfer, from the phase of tumor control to relapse. Using a preclinical model of noncurative lymphoma and samples from a responder and a nonresponder patient treated with CAR19/IL-15 NK cells, we observed the emergence of NK cell clusters with distinct patterns of activation, function, and metabolic signature associated with different phases of in vivo evolution and tumor control. Interaction with the highly metabolically active tumor resulted in loss of metabolic fitness in NK cells that could be partly overcome by incorporation of IL-15 in the CAR construct.

Keywords

Humans, Receptors, Chimeric Antigen, Interleukin-15, Cytokines, Cell Line, Tumor, Killer Cells, Natural, Cell- and Tissue-Based Therapy

DOI

10.1126/sciadv.add6997

PMID

37494448

PMCID

PMC10371011

PubMedCentral® Posted Date

July 2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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