Blood Cancer Journal (Apr 2024)
A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death
- Arghya Ray,
- Ting Du,
- Xueping Wan,
- Yan Song,
- Sindhu C. Pillai,
- Md. Abu Musa,
- Teng Fang,
- Jared Moore,
- Brian Blank,
- Xiaohui Du,
- Xi Chen,
- Robert Warne,
- Dena Sutimantanapi,
- Fang Lui,
- Tatiana Zavorotinskaya,
- Christophe Colas,
- Lori Friedman,
- Melissa R. Junttila,
- Dharminder Chauhan,
- Kenneth C. Anderson
Affiliations
- Arghya Ray
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Ting Du
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Xueping Wan
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Yan Song
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Sindhu C. Pillai
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Md. Abu Musa
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Teng Fang
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Jared Moore
- ORIC Pharmaceuticals, Inc.
- Brian Blank
- ORIC Pharmaceuticals, Inc.
- Xiaohui Du
- ORIC Pharmaceuticals, Inc.
- Xi Chen
- ORIC Pharmaceuticals, Inc.
- Robert Warne
- ORIC Pharmaceuticals, Inc.
- Dena Sutimantanapi
- ORIC Pharmaceuticals, Inc.
- Fang Lui
- ORIC Pharmaceuticals, Inc.
- Tatiana Zavorotinskaya
- ORIC Pharmaceuticals, Inc.
- Christophe Colas
- ORIC Pharmaceuticals, Inc.
- Lori Friedman
- ORIC Pharmaceuticals, Inc.
- Melissa R. Junttila
- ORIC Pharmaceuticals, Inc.
- Dharminder Chauhan
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- Kenneth C. Anderson
- The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
- DOI
- https://doi.org/10.1038/s41408-024-01019-5
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 6
Abstract
Highlights 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).