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

  • Blood Cancer J. 2024 Apr 9;14(1):58. doi: 10.1038/s41408-024-01019-5.
Arghya Ray  1 ,  Ting Du  2 ,  Xueping Wan  2 ,  Yan Song  2 ,  Sindhu C Pillai  2 ,  Md Abu Musa  2 ,  Teng Fang  2 ,  Jared Moore  3 ,  Brian Blank  3 ,  Xiaohui Du  3 ,  Xi Chen  3 ,  Robert Warne  3 ,  Dena Sutimantanapi  3 ,  Fang Lui  3 ,  Tatiana Zavorotinskaya  3 ,  Christophe Colas  3 ,  Lori Friedman  3 ,  Melissa R Junttila  3 ,  Dharminder Chauhan  #  4 ,  Kenneth C Anderson  #  5
Affiliations
  • 1. 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. [email protected].
  • 2. 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.
  • 3. ORIC Pharmaceuticals, Inc., South San Francisco, CA, USA.
  • 4. 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. [email protected].
  • 5. 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. [email protected].
  • # Contributed equally.
PMID: 38594241 DOI: 10.1038/s41408-024-01019-5
Abstract

  1. CD73 is the key ectoenzyme involved in the generation of AMP-derived Adenosine, which contributes to Immunosuppression in the MM BM milieu.

  2. 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.

  3. 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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