Varadarajan, Navin2023-06-02December 22022-12-13Portions of this document appear in: "T-cell potential for CD19-expressing malignancies revealed by multi-dimensional single-cell profiling," Ali Rezvan, Gabrielle Romain, Mohsen Fathi, Darren Heeke, Melisa Martinez-Paniagua, Xingyue An, Irfan N Bandey, Arash Saeedi, Fatemeh Sadeghi, Kristen Fousek, Nahum Puebla-Osorio, Laurence J.N. Cooper, Chantale Bernatchez, Harjeet Singh, Nabil Ahmed, Mike Mattie, Adrian Bot, Sattva Neelapu, Navin Varadarajan, bioRxiv 2022.06.22.497245; doi: https://doi.org/10.1101/2022.06.22.497245https://hdl.handle.net/10657/14408Chimeric antigen receptors (CAR) T cells for B-cell malignancies serve as a model for identifying T-cell subsets with superior clinical activity. We profiled the infusion products (IP) of patients with large B-cell lymphoma (LBCL) using multi-omic single-cell assays to reveal the therapeutic potential of CD19-CAR+ T cells. Functional profiling using timelapse imaging microscopy in nanowell grids (TIMING) profiling revealed that T cells from responders showed high migration and serial killing. Cellular profiling using confocal microscopy revealed that migration is correlated with both mitochondrial and lysosomal volume; and molecular profiling scRNA-seq demonstrated that T cells from responders were enriched in pathways related to T-cell killing, migration and actin cytoskeleton, and in vivo persistence. T cells enriched for migratory capacity showed sustained serial killing and optimal in vivo efficacy. Our results demonstrate that migration is a cell-intrinsic biomarker desired in the bioactivity of CAR+ T cells associated with clinical antitumor efficacy.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).Cell immunotherapyCAR T cells2023-06-02Thesisborn digital