

浏览全部资源
扫码关注微信
1.西湖大学医学院附属杭州市第一人民医院药学部/浙江省临床肿瘤药理与毒理学研究重点实验室,杭州 310006
2.浙江大学医学院附属第一医院胸外科,杭州 310003
3.浙江中医药大学药学院,杭州 311402
4.温州医科大学药学院,浙江 温州 325035
Received:27 May 2025,
Revised:2025-08-27,
Accepted:27 August 2025,
Published:15 October 2025
移动端阅览
林蒙蒙,林旭,王艺璇,等.双特异性抗体在肿瘤治疗中的临床应用及安全性研究进展[J].中国药房,2025,36(19):2466-2472.
LIN Mengmeng,LIN Xu,WANG Yixuan,et al.Advances in the clinical application and safety of bispecific antibodies for cancer therapy[J].ZHONGGUO YAOFANG,2025,36(19):2466-2472.
林蒙蒙,林旭,王艺璇,等.双特异性抗体在肿瘤治疗中的临床应用及安全性研究进展[J].中国药房,2025,36(19):2466-2472. DOI: 10.6039/j.issn.1001-0408.2025.19.19.
LIN Mengmeng,LIN Xu,WANG Yixuan,et al.Advances in the clinical application and safety of bispecific antibodies for cancer therapy[J].ZHONGGUO YAOFANG,2025,36(19):2466-2472. DOI: 10.6039/j.issn.1001-0408.2025.19.19.
双特异性抗体(BsAbs)作为近年来肿瘤免疫治疗领域的重要创新,可同时或依次靶向不同抗原或同一抗原的2个不同表位,相较于传统的单克隆抗体,能够产生更优的治疗效果。本文综述了BsAbs在肿瘤治疗中的临床应用及安全性研究进展,结果显示,该类药物(如贝林妥欧单抗、格菲妥单抗、特立妥单抗、埃万妥单抗等)对血液系统恶性肿瘤、肺癌、宫颈癌和黑色素瘤等具有显著疗效;针对BsAbs引发的细胞因子释放综合征,临床常采用预防性用药或前驱用药;针对BsAbs引发的神经毒性和感染,临床需严格监测患者体征,并提供必要治疗;另外,不同BsAbs在递增剂量、输注速度、储存时限和设备要求上存在差异,临床操作中需严格遵循药品说明书要求以确保安全与疗效。未来,需开展更多多中心试验验证BsAbs在不同肿瘤和患者群体中的疗效与安全性,积累长期随访数据以优化治疗周期和剂量方案。
Bispecific antibodies (BsAbs), as an important recent innovation in the field of tumor immunotherapy in recent years, can simultaneously or sequentially target different antigens or two different epitopes of the same antigen. Compared with traditional monoclonal antibodies, they can produce superior therapeutic effects. This article reviews the progress in clinical applications and safety research of BsAbs in cancer therapy, revealing that they (such as blinatumomab, glofitamab, teclistamab, amivantamab, etc.) exhibit significant therapeutic efficacy against hematological malignancies, lung cancer, cervical cancer, melanoma, and other cancers. For cytokine release syndrome (CRS) induced by BsAbs, prophylactic or pre-emptive medication is commonly administered in clinical practice; for neurotoxicity and infections triggered by BsAbs, clinical practice necessitates rigorous monitoring of patients’ vital signs and the provision of essential treatments. In addition, different BsAbs exhibit variations in escalation dose, infusion rate, storage duration, and equipment requirements. Therefore, strict adherence to the instructions in the drug package inserts is essential during clinical operations to ensure safety and therapeutic efficacy. In the future, more multicenter trials need to be conducted to validate the efficacy and safety of BsAbs across different tumor types and patient populations, and long-term follow-up data should be accumulated to optimize treatment cycles and dosage regimens.
BRAY F , LAVERSANNE M , SUNG H , et al . Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2024 , 74 ( 3 ): 229 - 263 .
KLEIN C , BRINKMANN U , REICHERT J M , et al . The present and future of bispecific antibodies for cancer therapy [J ] . Nat Rev Drug Discov , 2024 , 23 ( 4 ): 301 - 319 .
FUDENBERG H H , DREWS G , NISONOFF A . Serologic demonstration of dual specificity of rabbit bivalent hybrid antibody [J ] . J Exp Med , 1964 , 119 ( 1 ): 151 - 166 .
MILSTEIN C , CUELLO A C . Hybrid hybridomas and their use in immunohistochemistry [J ] . Nature , 1983 , 305 ( 5934 ): 537 - 540 .
STAERZ U D , KANAGAWA O , BEVAN M J . Hybrid antibodies can target sites for attack by T cells [J ] . Nature , 1985 , 314 ( 6012 ): 628 - 631 .
HERRERA M , PRETELLI G , DESAI J , et al . Bispecific antibodies:advancing precision oncology [J ] . Trends Cancer , 2024 , 10 ( 10 ): 893 - 919 .
LABRIJN A F , JANMAAT M L , REICHERT J M , et al . Bispecific antibodies:a mechanistic review of the pipeline [J ] . Nat Rev Drug Discov , 2019 , 18 ( 8 ): 585 - 608 .
SHAH B , MATTISON R J , ABBOUD R , et al . Acute lymphoblastic leukemia,version 2. 2024,NCCN clinical practice guidelines in oncology [J ] . J Natl Compr Canc Netw , 2024 , 22 ( 8 ): 563 - 576 .
李雪源 , 郭文璟 , 冯四洲 . Blinatumomab治疗急性B淋巴细胞白血病的研究进展 [J ] . 中国肿瘤临床 , 2023 , 50 ( 22 ): 1159 - 1163 .
王迪 , 赵成 , 徐晓军 . 贝林妥欧单抗治疗儿童急性淋巴细胞白血病的研究进展 [J ] . 中华儿科杂志 , 2024 , 62 ( 5 ): 482 - 485 .
KANTARJIAN H , STEIN A , GÖKBUGET N , et al . Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia [J ] . N Engl J Med , 2017 , 376 ( 9 ): 836 - 847 .
COUTURIER M A , THOMAS X , RAFFOUX E , et al . Blinatumomab + ponatinib for relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia in adults [J ] . Leuk Lymphoma , 2021 , 62 ( 3 ): 620 - 629 .
JABBOUR E J , SHORT N J , JAIN N , et al . Blinatumomab is associated with favorable outcomes in patients with B-cell lineage acute lymphoblastic leukemia and positive measurable residual disease at a threshold of 10 -4 and higher [J ] . Am J Hematol , 2022 , 97 ( 9 ): 1135 - 1141 .
BUDDE L E , SEHN L H , MATASAR M , et al . Safety and efficacy of mosunetuzumab,a bispecific antibody,in patients with relapsed or refractory follicular lymphoma:a single-arm,multicentre,phase 2 study [J ] . Lancet Oncol , 2022 , 23 ( 8 ): 1055 - 1065 .
DICKINSON M J , CARLO-STELLA C , MORSCHHAUSER F , et al . Glofitamab for relapsed or refractory diffuse large B-cell lymphoma [J ] . N Engl J Med , 2022 , 387 ( 24 ): 2220 - 2231 .
ABRAMSON J S , KU M , HERTZBERG M , et al . Glofi- tamab plus gemcitabine and oxaliplatin(GemOx)versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma(STARGLO):a global phase 3,randomised,open-label trial [J ] . Lancet , 2024 , 404 ( 10466 ): 1940 - 1954 .
HUTCHINGS M , MOUS R , CLAUSEN M R , et al . Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma:an open-label,phase 1/2 study [J ] . Lancet , 2021 , 398 ( 10306 ): 1157 - 1169 .
LINTON K M , VITOLO U , JURCZAK W , et al . Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma(EPCORE NHL-1):a phase 2 cohort of a single-arm,multicentre study [J ] . Lancet Haematol , 2024 , 11 ( 8 ): e593 - e605 .
韩帆 , 张雪鹏 , 席亚明 . 双特异性抗体在多发性骨髓瘤治疗中的研究进展 [J ] . 中国实验血液学杂志 , 2024 , 32 ( 3 ): 952 - 956 .
COHEN Y C , MAGEN H , GATT M , et al . Talquetamab plus teclistamab in relapsed or refractory multiple mye- loma [J ] . N Engl J Med , 2025 , 392 ( 2 ): 138 - 149 .
TOMASSON M H , IIDA S , NIESVIZKY R , et al . Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma:update from the MagnetisMM-3 study [J ] . Hemasphere , 2024 , 8 ( 7 ): e136 .
ZHOU C C , TANG K J , CHO B C , et al . Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions [J ] . N Engl J Med , 2023 , 389 ( 22 ): 2039 - 2051 .
CHOUAID C , BOSQUET L , KNOTT C , et al . Real-world frontline treatments in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions and adjusted comparisons versus amivantamab plus chemotherapy from the PAPILLON study [J ] . Lung Cancer , 2025 , 203 : 108548 .
WANG K W , DU R , MYALL N J , et al . Real-world efficacy and safety of amivantamab for EGFR-mutant NSCLC [J ] . J Thorac Oncol , 2024 , 19 ( 3 ): 500 - 506 .
DHILLON S . Ivonescimab:first approval [J ] . Drugs , 2024 , 84 ( 9 ): 1135 - 1142 .
XIONG A W , WANG L , CHEN J H , et al . Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer(HARMONi-2):a randomised,double-blind,phase 3 study in China [J ] . Lancet , 2025 , 405 ( 10481 ): 839 - 849 .
CHEN Z W , WU L , WANG Q M , et al . Brief report:ivonescimab combined with etoposide plus carboplatin as first-line treatment for extensive-stage SCLC:results of a phase 1b clinical trial [J ] . J Thorac Oncol , 2025 , 20 ( 2 ): 233 - 239 .
ZHANG Y X , HUANG Y , YANG Y P , et al . Iparomlimab and tuvonralimab(QL1706)plus chemotherapy and bevacizumab for EGFR-mutant patients with advanced non-small cell lung cancer after failure of EGFR-tyrosine kinase inhibitors:updated results from cohort 5 in the DUBHE-L-201 study [J ] . J Hematol Oncol , 2025 , 18 ( 1 ): 75 .
GAO X Y , XU N , LI Z Y , et al . Safety and antitumour activity of cadonilimab,an anti-PD-1/CTLA-4 bispecific antibody,for patients with advanced solid tumours(COMPASSION-03):a multicentre,open-label,phase 1b/2 trial [J ] . Lancet Oncol , 2023 , 24 ( 10 ): 1134 - 1146 .
CHEN J , YU H J , LIN Y T , et al . Real-world data of cadonilimab in recurrent or metastatic cervical cancer in China:a multicentric study [J ] . Front Immunol , 2025 , 16 : 1611696 .
CARVAJAL R D , SACCO J J , JAGER M J , et al . Advances in the clinical management of uveal melanoma [J ] . Nat Rev Clin Oncol , 2023 , 20 ( 2 ): 99 - 115 .
HASSEL J C , PIPERNO-NEUMANN S , RUTKOWSKI P , et al . Three-year overall survival with tebentafusp in metastatic uveal melanoma [J ] . N Engl J Med , 2023 , 389 ( 24 ): 2256 - 2266 .
LEE D W , GARDNER R , PORTER D L , et al . Current concepts in the diagnosis and management of cytokine release syndrome [J ] . Blood , 2014 , 124 ( 2 ): 188 - 195 .
FALCHI L , VARDHANA S A , SALLES G A . Bispecific antibodies for the treatment of B-cell lymphoma:promi- ses,unknowns,and opportunities [J ] . Blood , 2023 , 141 ( 5 ): 467 - 480 .
梁良 , 金鹏飞 , 王婷 , 等 . 托珠单抗治疗细胞因子释放综合征的文献分析 [J ] . 临床药物治疗杂志 , 2020 , 18 ( 3 ): 26 - 30 .
BRUDNO J N , KOCHENDERFER J N . Current understanding and management of CAR T cell-associated toxicities [J ] . Nat Rev Clin Oncol , 2024 , 21 ( 7 ): 501 - 521 .
FALCHI L , HUTCHINGS M , CARLO-STELLA C , et al . Dexamethasone is associated with reduced frequency and intensity of cytokine release syndrome compared with alternative corticosteroid regimens as premedication for glofitamab in patients with relapsed/refractory large B-cell lymphoma [J ] . Haematologica , 2025 , 110 ( 4 ): 999 - 1004 .
国家卫生健康委员会 . 血液肿瘤治疗药物的临床应用:2022版新型抗肿瘤药物临床应用指导原则:四 [J ] . 中国合理用药探索 , 2023 , 20 ( 7 ): 29 - 48 .
MORRIS E C , NEELAPU S S , GIAVRIDIS T , et al . Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy [J ] . Nat Rev Immunol , 2022 , 22 ( 2 ): 85 - 96 .
WATTANA M K , ROWLAND J , QDAISAT A , et al . Diagnosis and management of bispecific T cell-engaging antibody toxicity:a primer for emergency physicians [J ] . Cancer Treat Rev , 2025 , 134 : 102889 .
HAMMONS L , SZABO A , JANARDAN A , et al . The changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody(BsAb)therapy in patients with relapsed refractory multiple myeloma [J ] . Haematologica , 2024 , 109 ( 3 ): 906 - 914 .
JOURDES A , CELLERIN E , TOUZEAU C , et al . Characteristics and incidence of infections in patients with multiple myeloma treated by bispecific antibodies:a national retrospective study [J ] . Clin Microbiol Infect , 2024 , 30 ( 6 ): 764 - 771 .
GONUGUNTA A S , MOHLERE V , ABID M B . Risk of infections with bispecific antibodies in B-cell non-Hodgkin lymphomas and multiple myeloma:the current state [J ] . Br J Haematol , 2024 , 205 ( 3 ): 1197 - 1201 .
国家癌症中心 , 中国药师协会肿瘤专科药师分会 , 赫捷 , 等 . 抗体类抗肿瘤药物药学服务指南 [J ] . 中华肿瘤杂志 , 2022 , 44 ( 10 ): 1017 - 1046 .
0
Views
0
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
公网安备50010302001817