Deletion of CD38 enhances CD19 chimeric antigen receptor T cell function
Kimberly Veliz(University of Pennsylvania), Feng Shen(University of Pennsylvania), Olga Shestova(University of Pennsylvania), Maksim Shestov(University of Pennsylvania), Alexander A. Shestov(University of Pennsylvania), Sara Sleiman(University of Pennsylvania), Tyler Hansen(University of Pennsylvania), Roddy S. O’Connor(Parker Institute for Cancer Immunotherapy), Saar Gill(University of Pennsylvania)
Cited by 11Open Access
Abstract
. CD38 is a multifunctional ectoenzyme with hydrolase and cyclase activities. Reintroduction of CD38 mutants into T cells lacking CD38 provided further evidence supporting the understanding that CD38 plays a crucial role in producing the immunosuppressive metabolite adenosine and utilizing nicotinamide adenine dinucleotide (NAD) in human T cells. Taken together, these results highlight a role for CD38 as an immunometabolic checkpoint in T cells and lead us to propose CD38 deletion as an additional avenue for boosting CAR T cell function.
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