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A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death.

Blood Cancer J

April 2024

The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

CD73 is the key ectoenzyme involved in the generation of AMP-derived adenosine, which contributes to immunosuppression in the MM BM milieu. Blocking CD73 activity with a potent, selective, orally bioavailable CD73 inhibitor ORIC-533 decreases adenosine generation, overcomes immune suppression, and restores immune cell-mediated MM cell lysis. Based on these preclinical studies, a multi-center clinical trial of ORIC-533 has been initiated in patients with relapsed refractory MM (NCT05227144).

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