CHINESE JOURNAL OF MEDICINAL GUIDE >
Diversification of Antibody-Drug Conjugate （ADC） Targets and Their Applications in Tumor Treatment
Received date: 2024-12-17
Revised date: 2025-03-18
Accepted date: 2026-02-06
Online published: 2026-05-26
Chemotherapeutic agents face significant clinical constraints due to tumor drug resistance and severe adverse reactions caused by non-selective cytotoxicity. While novel anticancer therapies such as targeted drugs and immune checkpoint inhibitors have partially addressed these limitations， new challenges have emerged： targeted therapies are hindered by acquired resistance， rarely achieving long-term survival or cure through monotherapy. Immunotherapies exhibit delayed onset of action and often require combinatorial approaches with chemotherapy to enhance response rates.Antibody-drug conjugates （ADCs） represent a transformative breakthrough in oncology by covalently linking monoclonal antibodies to potent cytotoxic agents via cleavable or non-cleavable linkers. This innovative design achieves the integration of precision targeting and high-efficiency tumor eradication， addressing the long-standing challenge of balancing efficacy and toxicity in cancer treatment.The core advantages of ADCs lie in their ability to selectively deliver cytotoxic payloads to tumor cells， thereby minimizing systemic toxicity while amplifying therapeutic efficacy through the bystander effect. By unifying target specificity， structural stability， and synergistic potency， ADCs significantly improve the therapeutic risk-benefit ratio in anticancer interventions.In recent years， the diversification of ADC targets has expanded to cover multiple key tumor-associated antigens （e.g.， HER2， TROP2， CD79b）， driving groundbreaking innovations in clinical oncology. This study comprehensively analyzes the spectrum of target antigens， molecular mechanisms of action， and clinical therapeutic outcomes of globally approved ADCs， to establish a robust theoretical foundation and actionable strategies for advancing precision medicine in oncology， guiding both drug development and clinical practice.
Li Lei Lei
.
Diversification of Antibody-Drug
Conjugate （ADC） Targets and Their
Applications in Tumor Treatment
［1］ 曾弘烨，宁文静，罗文新.ADC药物的抗体组成及其作用靶点研究进展［J］.中国生物工程杂志，2022，42（5）：69-80.
［2］ Wang Wei， Erbe AK， Hank JA， et al. Antibody-dependent cellular cytotoxicity （ADCC）： mechanisms and role in cancer therapy［J］.J Immunother Cancer， 2015，3：37.
［3］ Hurvitz SA， Hegg R， Chung WP， et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer： updated results from DESTINY-Breast03， a randomised， open-label，phase 3 trial［J］.Lancet，2023，401（10371）： 105-110.
［4］ Ntanasis-Stathopoulos， I Dimopoulos MA.Treatment of early relapse： non-CAR T cells［J］.Clin Lymphoma Myeloma Leukemia，2024，24（1）： S96-S97.
［5］ Tilly H， Morschhauser F， Laurie HS， et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma［J］.N Engl J Med， 2022， 386（4）： 351-363.
［6］ Laurie HS， Alex FH，Christopherv RF， et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma［J］.J Clin Oncol， 2020，38（2）：155-165.
［7］ Powles T， Valderrama BP， Gupta S， et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer［J］.N Engl J Med， 2024，7，390（10）：875-888.
［8］ Sheng Xinan， Wang Li， He Zhihong， et al. Efficacy and safety of disitamab vedotin in patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic urothelial carcinoma：a combined analysis of two phase II clinical trials［J］.J Clin Oncol， 2024，42（12）：1391-1402.
［9］ 冯梓航，李南林，温鑫鑫.乳腺癌HER-2低表达人群的靶向治疗新选择研究进展［J］.中华肿瘤防治杂志，2023，4（26）：51-61.
［10］ 曹天助，牛庆田，刘兵，等.基于RTCA技术研究抗体偶联药物的旁观者效应的检测方法［J］.中南药学，2024，22（5）：1227-1231.
［11］ Shanu M， William J， Toshinari Y， et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer［J］.N Engl J Med， 2022，387（1）：9-20.
［12］ Teemu TJ， Li Guangmin.Trastuzumab-DMI（T-DMI） retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib intensive breast cancer［J］.Breast Cancer Res Treat， 2011，128：347-356.
［13］ Swain MS， Shastry M， Hamilton E. Targeting HER2-positive breast cancer： advances and future directions［J］.Nat Rev Drug Discov， 2023，22（2）：101-126.
［14］ Hurvitz SA， Hegg R， Chung WP， et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer： updated results from DESTINY-Breast03， a randomised， open-label， phase 3 trial［J］.Lancet，2023， 401（10371）：105-110.
［15］ Bardia A， Hurvitz SA，Tolaney SM， et al. Sacituzumab govitecan in metastatic triple-negative breast cancer［J］.N Engl J Med， 2021，384：29-41.
［16］ 王浩，黄佳，钟薇，等.靶向Trop-2的抗体偶联药物：戈沙妥珠单抗［J］.中国新药与临床杂志，2023，2（27）：36-45.
［17］ Moore KN， Angelergues A， Konecny GE， et al. Mirvetuximab soravtansine in FRα-positive，platinum-resistant ovarian cancer［J］.N Engl J Med， 2023，389（23）：2162-2174.
［18］ Coleman RL， Lorusso D， Gennigens C， et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer （innavaTV 204/GOG-3023/ENGOT-cx6）； a multicentre. open-label，single-arm ，phase 2 study［J］.Lancet Oncol， 2021，22：609-619.
［19］ Döhner H， Wei AH， Appelbaum FR， et al. Diagnosis and management of AML in adults： 2022 recommendations from an international expert panel on behalf of the ELN［J］. Blood， 2022，140（12）：1345-1377.
［20］ Castaigne S， Pautas C， Terré C， et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia （ALFA-0701）： a randomised， open-label， phase 3 study［J］.Lancet， 2012，379（9825）：1508-1516.
［21］ Bazinet A， Kantarjian HM. Moving toward individualized target-based therapies in acute myeloid leukemia［J］. Ann Oncol， 2023，34（2）：141-151.
［22］ Short NJ， Jabbour E， Jain N， et al. Inotuzumab ozogamicin for the treatment of adult acute lymphoblastic leukemia： past progress， current research and future directions ［J］. J Hematol Oncol， 2024，17（1）：32.
［23］ Pagano L， Criscuolo M， Broccoli A， et al. Long-term follow-up of cladribine treatment in hairy cell leukemia： 30-year experience in a multicentric Italian study［J］.Blood Cancer J， 2022，12（7）： 109.
［24］ Herrera AF， Zain J， Savage KJ，et al. Brentuximab vedotin plus cyclophosphamide， doxorubicin， etoposide， and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas： a multicentre， single-arm， phase 2 study［J］.Lancet Haematol， 2024，11（9）：e671-e681.
［25］ Burger JA， Wiestner A. Targeting B cell receptor signalling in cancer： preclinical and clinical advances［J］.Nat Rev Cancer， 2018，18（3）：148-167.
［26］ Tilly H， Morschhauser F， Sehn LH， et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma［J］.N Engl J Med， 2022，386（4）：351-363.
［27］ Sehn LH， Herrera AF， Flowers CR，et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma［J］.J Clin Oncol， 2020，38（2）： 155-165.
［28］ Lin Ningjing， Sun Xiuhua， Zhou Hui， et al.Loncastuximab tesirine in Chinese patients with relapsed or refractory diffuse large B-cell lymphoma： a multicenter， open-label， single-arm， phase II trial［J］.Haematologica， 2025， 110（3）：683-692.
［29］ Dimopoulos MA， Beksac M， Pour L， et al.Belantamab mafodotin，pomalidomide，and dexamethasone in multiple myeloma［J］.N Eng J Med， 2024，391（5）：408-421.
［30］ Bang YJ， van Cutsem E， Feyereislova A， et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer （ToGA）： a phase 3， open-label， andomized controlled trial［J］. Lancet，2010，376（9742）：687-697.
［31］ Sheng Xinan， Wang Li， He Zhihong， et al. Efficacy and safety of disitamab vedotin in patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic urothelial carcinoma：a combined analysis of two phase II clinical trials［J］.J Clin Oncol， 2023，21：JCO2202912.
［32］ Tan Hongni， Chen Yingchun， Liu Zhihui， et al. Treatment-related adverse events of antibody drug-conjugates in clinical trials：a systematic review and meta-analysis［J］.Haematologica， 2025，18（1）：45.
［33］ Wong Minghuang， Chen Tingyu， Huang Chichen， et al. Antibody-drug conjugates： new drugs-new toxicities：a systematic review of emerging safety signals［J］.Curr Opin Oncol， 2026，38（2）：120-128.
［34］ Jain MD， Abramson JS， Ansell SM， et al. Easy as ABC：managing toxicities of antibody-drug conjugates， bispecific antibodies， and CAR T-Cell therapies［J］.Am Soc Clin Oncol Educ Book， 2025，45（3）：e473916.
［35］ Jaffry M， Choudhry H， Aftab OM， et al. Antibody-drug conjugates and ocular toxicities［J］.J Ocul Pharmacol Ther， 2023，39（10）：675-691.
［36］ Jonathan R， Sridhar SS， Zhang Jing， et al. EV-101： a phase I study of single-agent enfortumab vedotin in patients with nectin-4-positive solid tumors， including metastatic urothelialcarcinoma［J］.J Clin Oncol， 2020，38（10）：1041-1049.
［37］ Haleh S， Nicole S， Ricks TK， et al. An FDA oncology analysis of toxicities associated with PBD-containing antibody-drug conjugates［J］.Regul Toxicol Pharmacol， 2019，107：104429.
［38］ Fisher JE Jr. Considerations for the nonclinical safety evaluation of antibody-drug conjugates［J］. Antibodies （Basel）， 2021，10（2）：15.
［39］ Lu Jun， Jiang Feng， Lu Aiping， et al. Linkers having a crucial role in antibody-drug conjugates［J］.Int J Mol Sci， 2016，17（4）：561.
［40］ Mahalingaiah PK， Ciurlionis R， Durbin KR， et al.Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates［J］.Pharmacol Ther， 2019，200：110-125.
/
| 〈 |
|
〉 |