Faculty, Staff and Student Publications

Publication Date

9-1-2022

Journal

Journal of Clinical Investigation

Abstract

The in vivo persistence of adoptively transferred T cells is predictive of antitumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific chimeric antigen receptor (CAR) T cells as the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on time-lapse imaging microscopy in nanowell grids (TIMING), which integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with multifunctionality. We showed that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing. Consistent with this, we observed that elevated CD58 expression on pretreatment tumor samples in patients with relapsed or refractory large B cell lymphomas treated with CD19-specific CAR T cell therapy was associated with complete clinical response and survival. These results highlight the importance of studying dynamic T cell-tumor cell interactions in identifying optimal antitumor responses.

Keywords

Antigens, CD19, CD2 Antigens, CD58 Antigens, Humans, Immunotherapy, Adoptive, Lymphoma, Large B-Cell, Diffuse, Receptors, Antigen, T-Cell, Single-Cell Analysis, T-Lymphocytes, Cancer immunotherapy, Immunology, Oncology

DOI

10.1172/JCI159402

PMID

35881486

PMCID

PMC9433104

PubMedCentral® Posted Date

9-1-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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