[CCoE Notice] Cullen College Dissertation Defense Announcement - Ali Rezvan

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[Dissertation Defense Announcement at the Cullen College of Engineering]

Functional metrics of efficacious CAR T cells revealed by multi-dimensional single-cell profiling



Ali Rezvan

November 30, 2022;  12:00 PM – 2:00 PM (CST)

Zoom: https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/98348502418?pwd=eXdCc3U1QnJTVVZJZE1FalVHNGo0dz09__;!!LkSTlj0I!AgMO3PjDmMI_JnMNdB2ODxqWfHgR0h-gec4cYY_dJns5lBQx8f8IJu14hz80FoO7jmApoK7Czk1gbsCmf6GK0wWdpf0$ 





Committee Chair:
Navin Varadarajan, PhD

Committee Members:
Richard Willson, Ph.D. | Jacinta Conrad, Ph.D. | Chandra Mohan, Ph.D. | Harjeet Singh, PhD. |

Shaun Xiaoliu Zhang, PhD.

Abstract

Chimeric 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.

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