靶向CD47治疗髓系肿瘤的相关进展

沈一凡; 吴徳沛; 徐杨

doi:10.13201/j.issn.1004-2806.2022.09.017

靶向CD47治疗髓系肿瘤的相关进展

- 苏州大学附属第一医院，国家血液系统疾病临床医学研究中心，江苏省血液研究所，卫生部血栓与止血重点实验室，苏州大学造血干细胞移植研究所(江苏苏州，215006)
基金项目:
国家重点研发计划(No：2019YFC0840604)

详细信息

通讯作者: 徐杨，E-mail：Yangxu@suda.edu.cn

中图分类号: R733

收稿日期: 2022-03-13

刊出日期: 2022-09-01

Advances in targeting CD47 in the treatment of myeloid malignancies

- The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, 215006, China

More Information

Corresponding author: XU Yang, E-mail: Yangxu@suda.edu.cn

Received Date: 13 March 2022

Publish Date: 01 September 2022

摘要

摘要: CD47作为“don't eat me”信号在髓系肿瘤表面表达上调，可与巨噬细胞上信号调节蛋白α相结合抑制巨噬细胞吞噬功能，在肿瘤细胞的免疫逃避中起作用。有研究表明，CD47高表达与骨髓增生异常综合征的进展及急性髓系白血病的不良预后相关。CD47作为固有免疫中备受瞩目的免疫检查点，靶向CD47治疗髓系肿瘤的多种药物目前已经进入临床试验阶段，有望成为治疗髓系肿瘤的强有力手段。
- CD47-SIRPα /
- 髓系肿瘤 /
- 免疫机制 /
- CD47特异性抗体 /
- SIRPα融合蛋白
Abstract: As the "don't eat me" signal, CD47 is upregulated on the surface of myeloid malignancies and binds to signal regulatory protein alpha on macrophages to inhibit macrophage phagocytosis, and play a role in the immune evasion of malignancy cells. Studies have shown that high expression of CD47 is associated with the progression of myelodysplastic syndrome and poor prognosis in acute myeloid leukemia. CD47 is a high-profile immune checkpoint in innate immunity, and a variety of drugs targeting CD47 for the treatment of myeloid malignancies have entered the stage of clinical trial. Related drugs are expected to become a powerful means of treating myeloid malignancies.
- CD47-SIRPα /
- myeloid malignancies /
- immune mechanism /
- CD47 specific antibody /
- SIRPα fusion protein

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参考文献(33)

[1]	Piccione EC, Juarez S, Liu J, et al. A bispecific antibody targeting CD47 and CD20 selectively binds and eliminates dual antigen expressing lymphoma cells[J]. MAbs, 2015, 7(5): 946-956. doi: 10.1080/19420862.2015.1062192
[2]	Majeti R, Chao MP, Alizadeh AA, et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells[J]. Cell, 2009, 138(2): 286-299. doi: 10.1016/j.cell.2009.05.045
[3]	Rinaldi CR, Boasman K, Simmonds M, et al. Abstract 7557: Expression of CD47 and CALR in myeloproliferative neoplasms and myelodysplastic syndrome: potential new therapeutical targets[J]. J Clin Oncol, 2019, 38(15): 7557.
[4]	朱孔黎, 王艳萍, 宋海燕. CD47分子在抗肿瘤免疫中的应用[J]. 中国新药与临床杂志, 2020, 39(6): 335-341. https://www.cnki.com.cn/Article/CJFDTOTAL-XYYL202006004.htm
[5]	王艳煜, 赵维莅. 靶向清除白血病干细胞的研究进展[J]. 临床血液学杂志, 2013, 26(5): 343-337. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ201305022.htm
[6]	Femg MY, Jiang W, Kim BYS, et al. Phagocytosis checkpoints as new targets for cancer immunotherapy[J]. Nat Rev Cancer, 2019, 19(10): 568-586. doi: 10.1038/s41568-019-0183-z
[7]	Oldenborg PA, Zheleznyak A, Fang YF, et al. Role of CD47 as a Marker of Self on Red Blood Cells[J]. Science, 2000, 288(5473): 2051-2054. doi: 10.1126/science.288.5473.2051
[8]	Logtenberg MEW, Scheeren FA, Schumacher TN. The CD47-SIRPα immune checkpoint[J]. Immunity, 2020, 52(5): 742-752. doi: 10.1016/j.immuni.2020.04.011
[9]	Xu MM, Pu Y, Han DL, et al. Dendritic cells but not macrophages sense tumor mitochondrial DNA for cross-priming through Signal Regulatory Protein α signaling[J]. Immunity, 2017, 47: 363-373. doi: 10.1016/j.immuni.2017.07.016
[10]	Feng MY, Chen JY, Weissman-Tsukamoto R, et al. Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk[J]. Proc Natl Acad Sci U S A, 2015, 112(7): 2145-2150. doi: 10.1073/pnas.1424907112
[11]	Traver D, Akashi K, Weissman IL, et al. Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia[J]. Immunity, 1998, 9(1): 47-57. doi: 10.1016/S1074-7613(00)80587-7
[12]	王颖超, 冯磊, 殷楚云, 等. 抗CD47抗体联合阿糖胞苷靶向治疗NOD/SCID小鼠单核细胞白血病的研究[J]. 中国当代儿科杂志, 2013, 15(7): 577-582. https://www.cnki.com.cn/Article/CJFDTOTAL-DDKZ201307020.htm
[13]	Tahk S, Vick B, Hiller B, et al. SIRPα-αCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AML-initiating cells[J]. J Hematol Oncol, 2021, 14(1): 155. doi: 10.1186/s13045-021-01163-6
[14]	Dong XF, Hu Y, Han Y, et al. Phagocytosis checkpoints on hematopoietic stem cells in patients with myelodysplastic syndromes[J]. Asia Pac J Clin Onco, 2021, 18(2): 119-128.
[15]	Yan X, Lai BB, Zhou XY, et al. The Differential Expression of CD47 may be Related to the Pathogenesis From Myelodysplastic Syndromes to Acute Myeloid Leukemia[J]. Front Oncol, 2022, 12: 872999. doi: 10.3389/fonc.2022.872999
[16]	Chao MP, Takimoto CH, Feng DD, et al. Therapeutic targeting of the macrophage immune checkpoint CD47 in myeloid malignancies[J]. Front Oncol, 2020, 9: 1380. doi: 10.3389/fonc.2019.01380
[17]	Liu Y, Bewersdorf JP, Stah M, et al. Immunotherapy in acute myeloid leukemia and myelodysplastic syndromes: The dawn of a new era?[J]. Blood Rev, 2019, 34: 67-83. doi: 10.1016/j.blre.2018.12.001
[18]	Jiang HJ, Fu R, Wang HQ, et al. CD47 is expressed abnormally on hematopoietic cells in myelodysplastic syndrome[J]. Leuk Res, 2013, 37(8): 907-910. doi: 10.1016/j.leukres.2013.04.008
[19]	Advani R, Flinn I, Popplewell L, et al. CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin's lymphoma[J]. N Engl J Med, 2018, 379(18): 1711-1721. doi: 10.1056/NEJMoa1807315
[20]	Sallman DA, Donnellan WB, Asch AS, et al. Abstract 7009: the first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: Initial phase 1b results[J]. J Clin Oncol, 2019, 37(15): 7009.
[21]	Obeid M, Panaretakis T, Tesniere A, et al. Leveraging the Immune System during Chemotherapy: Moving Calreticulin to the Cell Surface Converts Apoptotic Death from "Silent" to Immunogenic[J]. Cancer Res, 2007, 67(17): 7941-7944. doi: 10.1158/0008-5472.CAN-07-1622
[22]	Sallman DA, Asch AS, Al Malki MM, et al. Abstract 569: the first-in-class anti-CD47 antibody magrolimab(5F9) in combination with azacitidine Is effective in MDS and AML patients: ongoing phase 1b results[J]. Blood, 2019, 134: 569. doi: 10.1182/blood-2019-126271
[23]	Ni HQ, Cao L, Wu ZH, et al. Combined strategies for effective cancer immunotherapy with a novel anti-CD47 monoclonal antibody[J]. Cancer Immunol Immunother, 2022, 71(2): 353-363. doi: 10.1007/s00262-021-02989-2
[24]	Gan HK, Coward J, Mislang ARA, et al. Abstract 2630: safety of AK117, an anti-CD47 monoclonal antibody, in patients with advanced or metastatic solid tumors in a phase Ⅰ study[J]. J Clin Oncol, 2021, 39(15): 2630.
[25]	Qi JY, Li J, Jiang B, et al. Abstract: A Phase Ⅰ/Ⅱa Study of Lemzoparlimab, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory Acute Myeloid Leukemia(AML)and Myelodysplastic Syndrome(MDS): Initial Phase Ⅰ Results[J]. Blood, 2020, 136: 30-31.
[26]	高向征, 梁可莹, 梅圣圣, 等. 联合靶向免疫检查点CD47与PDL1的抗肿瘤研究进展[J]. 中国细胞生物学学报, 2021, 43(4): 896-904. https://www.cnki.com.cn/Article/CJFDTOTAL-XBZZ202104024.htm
[27]	Wang Y, Ni HQ, Zhou SX, et al. Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity[J]. Cancer Immunol Immunother, 2021, 70(2): 365-376. doi: 10.1007/s00262-020-02679-5
[28]	Petrova PS, Viller NN, Wong M, et al. TTI-621(SIRPαFc): a CD47-blocking innate immune checkpoint inhibitor with broad antitumor activity and minimal erythrocyte binding[J]. Clin Cancer Res, 2017, 23(4): 1068-1079. doi: 10.1158/1078-0432.CCR-16-1700
[29]	Ansell SM, Maris MB, Lesokhin AM, et al. Phase Ⅰ study of the CD47 blocker TTI-621 in patients with relapsed or refractory hematologic malignancies[J]. Clin Cancer Res, 2021, 27(8): 2190-2199. doi: 10.1158/1078-0432.CCR-20-3706
[30]	Patel K, Ramchandren R, Maris M, et al. Investigational CD47-blocker TTI-622 shows single-agent activity in patients with advanced relapsed or refractory lymphoma: update from the ongoing first-in-human dose escalation study[J]. Blood, 2020, 136: 46-47.
[31]	Kim TY, Yoon MS, Hustinx H, et al. Assessing and mitigating the interference of ALX148, a novel CD47 blocking agent, in pretransfusion compatibility testing[J]. Transfusion, 2020, 60(10): 2399-2407. doi: 10.1111/trf.16009
[32]	Kauder SE, Kuo TC, Harrabi O, et al. ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile[J]. PLoS One, 2018, 13(8): e0201832. doi: 10.1371/journal.pone.0201832
[33]	Kim TM, Lakhani N, Gainor J, et al. Abstract 4180: a phase 1 study of ALX148, a CD47 blocker, in combination with rituximab in patients with non-Hodgkin lymphoma[J]. Blood, 2019, 134(1): 4180.