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

被引：4

作者：

Ray, Arghya ^{[1
,2
]}

Du, Ting ^{[1
,2
]}

Wan, Xueping ^{[1
,2
]}

Song, Yan ^{[1
,2
]}

Pillai, Sindhu C. ^{[1
,2
]}

Musa, Md. Abu ^{[1
,2
]}

Fang, Teng ^{[1
,2
]}

Moore, Jared ^{[3
]}

Blank, Brian ^{[3
]}

Du, Xiaohui ^{[3
]}

Chen, Xi ^{[3
]}

Warne, Robert ^{[3
]}

Sutimantanapi, Dena ^{[3
]}

Lui, Fang ^{[3
]}

Zavorotinskaya, Tatiana ^{[3
]}

Colas, Christophe ^{[3
]}

Friedman, Lori ^{[3
]}

Junttila, Melissa R. ^{[3
]}

Chauhan, Dharminder ^{[1
,2
]}

Anderson, Kenneth C. ^{[1
,2
]}

机构：

[1] Harvard Med Sch, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA

[2] Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA

[3] ORIC Pharmaceut Inc, South San Francisco, CA USA

来源：

BLOOD CANCER JOURNAL | 2024年 / 14卷 / 01期

基金：

美国国家卫生研究院;

关键词：

T-CELLS; COMBINATION; CHECKPOINT; ADENOSINE; CANCER;

D O I：

10.1038/s41408-024-01019-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

center dot CD73 is the key ectoenzyme involved in the generation of AMP-derived adenosine, which contributes to immunosuppression in the MM BM milieu. center dot 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. center dot Based on these preclinical studies, a multi-center clinical trial of ORIC-533 has been initiated in patients with relapsed refractory MM (NCT05227144).

引用

页数：6

共 50 条

[1] Targeting CD73 with AB680 (Quemliclustat), a Novel and Potent Small-Molecule CD73 Inhibitor, Restores Immune Functionality and Facilitates Antitumor Immunity
Piovesan, Dana
Tan, Joanne B. L.
Becker, Annette
Banuelos, Jesus
Narasappa, Nell
DiRenzo, Daniel
Zhang, Kristen
Chen, Ada
Ginn, Elaine
Udyavar, Akshata R.
Yin, Fangfang
Paprcka, Susan L.
Purandare, Bhamini
Park, Timothy W.
Kimura, Nikki
Kalisiak, Jaroslaw
Young, Stephen W.
Powers, Jay P.
Schindler, Uli
Sivick, Kelsey E.
Walters, Matthew J.
MOLECULAR CANCER THERAPEUTICS, 2022, 21 (06) : 948 - 959
[2] CD73 Inhibition Overcomes Immunosuppression and Triggers Autologous T-Cell Mediated Multiple Myeloma Cell Lysis in the Bone Marrow Milieu
Ray, Arghya
Junttila, Melissa R.
DU, Ting
Sutimantanapi, Dena
Chen, Xi
Warne, Bob
Chang, Jae
Blank, Brian
Wu, Kejia
Moore, Jared
Ndubaku, Chudi
Zavorotinskaya, Tatiana
Nadeem, Omar
Friedman, Lori
Chauhan, Dharminder
Anderson, Kenneth C.
BLOOD, 2021, 138
[3] Role of ectoenzymes CD39 and CD73 in the immune response to multiple myeloma
Yang, Rui
Elsaadi, Samah
Misund, Kristine
Slupphaug, Geir
Menu, Eline
Hay, Carl
Cooper, Zac
Vanderkerken, Karin
Borset, Magne
Sponaas, Anne Marit
CANCER RESEARCH, 2018, 78 (13)
[4] Reversal of adenosine-mediated immune suppression by AB421, a potent and selective small-molecule CD73 inhibitor
Tan, Joanne B. L.
Becker, Annette
DiRenzo, Daniel
Zhang, Kristen
Chen, Ada
Thomas-Tran, Rhiannon
Beatty, Joel
Mandal, Debashis
Xu, Guifen
Young, Steve
Walters, Matthew
Schindler, Ulrike
Powers, Jay
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2017, 5
[5] Reversal of adenosine-mediated immune suppression by CB-708, an orally bioavailable and potent small molecule inhibitor of CD73
Lee, Clarissa C.
Bhupathi, Deepthi
Billedeau, Roland J.
Chen, Jason
Chen, Lijing
Emberley, Ethan D.
Gross, Matthew I.
Huang, Tony
Li, Weiqun
Ma, Yong
Mackinnon, Andrew L.
Makkouk, Amani
Marguier, Gisele M.
Neou, Silinda
Parlati, Francesco
Sotirovska, Natalija
Stanton, Timothy F.
Steggerda, Susanne M.
Zhang, Jing
Zhang, Winter
Li, Jim
CANCER RESEARCH, 2019, 79 (13)
[6] AB680, a potent and selective CD73 small molecule inhibitor, reverses the AMP/adenosine-mediated impairment of immune effector cell activation by immune checkpoint inhibitors
Schindler, U.
Becker, A.
Lawson, K.
Jin, L.
Jeffrey, J.
Kalisiak, J.
Yin, F.
Zhang, K.
Chen, A.
Swinarski, D.
Walters, M. J.
Young, S.
Powers, J. P.
Tan, J.
EUROPEAN JOURNAL OF CANCER, 2018, 92 : S14 - S14
[7] A novel multi-targeted small molecule inhibitor RGB 286638 triggers apoptosis and necrosis in multiple myeloma via dual cell death pathways
Cirstea, Diana
Hideshima, Teru
Santo, Loredana
Vallet, Sonia
Pozzi, Samantha
Vaghela, Nileshwari
Ikeda, Hiroshi
Patel, Kishan
Loferer, Hannes
Gorgun, Gullu
Perrone, Giulia
Calabrese, Elisabetta
Munshi, Nikhil
Anderson, Kenneth
Raje, Noopur
CANCER RESEARCH, 2009, 69
[8] ORIC-533, a small molecule CD73 inhibitor with best-in-class properties, reversesimmunosuppression and has potential as an immunomodulatory therapy in patients with multiple myeloma
Junttila, Melissa R.
Ray, Arghya
Warne, Robert
Chen, Xi
Du, Ting
Sutimantanapi, Dena
Chang, Jae H.
Blank, Brian
Moore, Jared
Ndubaku, Chudi O.
Zavorotinskaya, Tatiana
Multani, Pratik
Nadeem, Omar
Chauhan, Dharminder
Anderson, Kenneth C.
Friedman, Lori S.
CANCER RESEARCH, 2022, 82 (12)
[9] Identification of CD73 and A2AR/CD73 small molecule inhibitors for cancer immunotherapy as single agents or in combination with Immune-checkpoint therapies
Fons, Pierre
Bell, Andrew
Esquerre, Michael
Versluys, Stephanie
Bertrand, Florie
Schreyer, Adrian
Hopkins-Navratilova, Iva
Hernani, Leonardo-Silvestre
Bergeaud, Celia
Poussereau-Pomie, Celine
Marchand, Ghislaine
Robinson, Sean
Culurgioni, Simone
Cox, Richard
Besnard, Jeremy
Payne, Andrew
Ray, Peter
Pelissier, Emilie
Paillasse, Michael
Lisztwan, Joanna
Johnstone, Craig
Whittaker, Mark
Hopkins, Andrew
CANCER RESEARCH, 2019, 79 (13)
[10] A Novel Mechanism of B Cell-Mediated Immune Suppression through CD73 Expression and Adenosine Production
Kaku, Hiroaki
Cheng, Kai Fan
Al-Abed, Yousef
Rothstein, Thomas L.
JOURNAL OF IMMUNOLOGY, 2014, 193 (12): : 5904 - 5913

← 1 2 3 4 5 →