Selective targeting of CD38 hydrolase and cyclase activity as an approach to immunostimulation.

ABSTRACT: The ectoenzyme CD38 is highly expressed on the surface of mature immune cells, where they are a marker for cell activation, and also on the surface of multiple tumor cells such as multiple myeloma (MM). CD38-targeted monoclonal antibodies (MABs) such as daratumumab and isatuximab bind to CD38 and promote cancer cell death by stimulating the antitumor immune response. Although MABs are achieving unprecedented success in a percentage of cases, high rates of resistance limit their efficacy. Formation of the immunosuppressive intermediate adenosine is a major route by which this resistance is mediated. Thus there is an urgent need for small molecule agents that boost the immune response in T-cells. Importantly, CD38 is a dual-function enzyme, serving as a hydrolase and a nicotinamide adenine d

SUBMITTER: Benton TZ 

PROVIDER: S-EPMC9042253 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature