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A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death
Blood Cancer Journal ( IF 12.8 ) Pub Date : 2024-04-09 , DOI: 10.1038/s41408-024-01019-5
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

  • 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).



中文翻译:

一种新型 CD73 小分子抑制剂触发免疫介导的多发性骨髓瘤细胞死亡

  • CD73 是参与 AMP 衍生腺苷生成的关键胞外酶,有助于 MM BM 环境中的免疫抑制。

  • 使用强效、选择性、口服生物可利用的 CD73 抑制剂 ORIC-533 阻断 CD73 活性,可减少腺苷生成,克服免疫抑制,并恢复免疫细胞介导的 MM 细胞裂解。

  • 基于这些临床前研究,ORIC-533的多中心临床试验已在复发难治性多发性骨髓瘤患者中启动(NCT05227144)。

更新日期:2024-04-09
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