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
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons