多发性骨髓瘤新兴疗法的治疗进展

李 楠, 耿 惠
青海大学附属医院

摘要


多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，由产生免疫球蛋白的浆细胞在骨髓和/或髓外部位克隆扩
增引起。尽管MM治疗范式最近取得了许多进展，但目前的疗法显示出有限的长期有效性，最终疾病复发仍然非常
普遍。骨髓瘤细胞通常通过克隆进化和细胞信号通路的改变产生耐药性。因此，继续研究MM的新靶点对于规避累
积的耐药性、克服治疗限制性毒性和改善这种不治之症的预后至关重要。本文将从NK细胞疗法、蛋白水解靶向嵌
合体、肽基脯氨酰异构酶A（PPIA）、细胞周期蛋白依赖性激酶6（CDK6）等新兴疗法的前景进行概述。

关键词


多发性骨髓瘤；免疫疗法；新兴疗法

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参考


[1]沈子悦，陈建斌.多发性骨髓瘤免疫微环境及免

疫治疗概述.中国医药.2024.19（10）：1581-1585.

[2]Dima D, Ullah F, Mazzoni S, et al. Management of

relapsed–refractory multiple myeloma in the era of advanced

therapies: evidence-based recommendations for routine

clinical practice. Cancers. 2023. 15(7): 2160.

[3]Markouli M, Ullah F, Unlu S, et al. Toxicity profile

of chimeric antigen receptor T-cell and bispecific antibody

therapies in multiple myeloma: pathogenesis, prevention and

management. Current Oncology. 2023. 30(7): 6330-6352.

[4]韩帆，席亚明.NK细胞疗法在多发性骨髓瘤治

疗中的研究进展.中国实验血液学杂志.2024.32（01）：

297-301.

[5]Leivas A, Perez-Martinez A, Blanchard MJ, et al.

Novel treatment strategy with autologous activated and

expanded natural killer cells plus anti-myeloma drugs for

multiple myeloma. Oncoimmunology. 2016. 5(12): e1250051.

[6]Nahi H, Chrobok M, Meinke S, et al. Autologous

NK cells as consolidation therapy following stem cell

transplantation in multiple myeloma. Cell Reports Medicine.

2022. 3(2).

[7]Achilli S, Berthet N, Renaudet O. Antibody

recruiting molecules (ARMs): synthetic immunotherapeutics

to fight cancer. RSC Chemical Biology. 2021. 2(3): 713-724.

[8]Birch GC, Vergara-Cadavid J, Maqbool M, et al.

Expansion, persistence, and characteristics of autologous,

Bhv-1100 armored memory-like NK cells infused prior to

autologous stem cell transplant in MRD+ multiple myeloma

patients: a first-in-human trial. BLOOD. 2023. 142: 2105.

Advances in Mordern Medical

[9]Cao Z, Yang C, Wang Y, et al. Allogeneic CARNK cell therapy targeting both BCMA and GPRC5D

for the treatment of multiple myeloma. BLOOD. 2022.

140(Supplement 1): 7378-7378.

[10]Reiser J, Chan SR, Mathavan K, et al. FT555: offthe-shelf CAR-NK cell therapy co-targeting GPRC5D

and CD38 for the treatment of multiple myeloma. BLOOD.

2022. 140(Supplement 1): 4560-4561.

[11]Lin P, Silva FCR, Lin P, et al. CD70 CAR NK cells

in the treatment of multiple Myeloma. BLOOD. 2023. 142:

3463.

[12]Zhang X, Lee HC, Shirazi F, et al. Protein targeting

chimeric molecules specific for bromodomain and extraterminal motif family proteins are active against pre-clinical

models of multiple myeloma. LEUKEMIA. 2018. 32(10):

2224-2239.

[13]Lim SL, Damnernsawad A, Shyamsunder P, et

al. Proteolysis targeting chimeric molecules as therapy for

multiple myeloma: efficacy, biomarker and drug combinations.

HAEMATOLOGICA. 2019. 104(6): 1209.

[14]Lu X, Sabbasani VR, Osei-Amponsa V, et al.

Structure-guided bifunctional molecules hit a DEUBADlacking hRpn13 species upregulated in multiple myeloma.

Nature Communications. 2021. 12(1): 7318.

[15]Qiao J, Liu Y, Nian L, et al. The Resistance

Mechanism to BET-Protac in Multiple Myeloma. BLOOD.

2023. 142: 6584.

[16]Nigro P, Pompilio G, Capogrossi MC. Cyclophilin

A: a key player for human disease. Cell Death & Disease.

2013. 4(10): e888-e888.

[17]Lee J, Kim SS. Current implications of cyclophilins

in human cancers. JOURNAL OF EXPERIMENTAL &

CLINICAL CANCER RESEARCH. 2010. 29: 1-6.

[18]Cohen YC, Zada M, Wang S, et al. Identification of

resistance pathways and therapeutic targets in relapsed multiple

myeloma patients through single-cell sequencing. NATURE

MEDICINE. 2021. 27(3): 491-503.

[19]Tadesse S, Yu M, Kumarasiri M, Le BT, Wang S.

Targeting CDK6 in cancer: State of the art and new insights.

CELL CYCLE. 2015. 14(20): 3220-3230.

[20]Ng YLD, Ramberger E, Bohl SR, et al. Proteomic

profiling reveals CDK6 upregulation as a targetable resistance

mechanism for lenalidomide in multiple myeloma. Nature

Communications. 2022. 13(1): 1009.


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