h3B7A-LDM, a novel anti-mesothelin antibody-drug conjugate with the potential to induce antitumor immunity, shows potent efficacy against solid tumors

Dan-dan Zhou; Zi-hui Xie; Ai-jun Duan; Shi-yu Zhu; Ying Wang; Yong-su Zhen; Rui-Juan Gao; Qing-Fang Miao

doi:10.1016/j.jpha.2026.101550

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Dan-dan Zhou, Zi-hui Xie, Ai-jun Duan, Shi-yu Zhu, Ying Wang, Yong-su Zhen, Rui-Juan Gao, Qing-Fang Miao. h3B7A-LDM, a novel anti-mesothelin antibody-drug conjugate with the potential to induce antitumor immunity, shows potent efficacy against solid tumors[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101550

Citation:

Dan-dan Zhou, Zi-hui Xie, Ai-jun Duan, Shi-yu Zhu, Ying Wang, Yong-su Zhen, Rui-Juan Gao, Qing-Fang Miao. h3B7A-LDM, a novel anti-mesothelin antibody-drug conjugate with the potential to induce antitumor immunity, shows potent efficacy against solid tumors[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101550

Citation:

Dan-dan Zhou, Zi-hui Xie, Ai-jun Duan, Shi-yu Zhu, Ying Wang, Yong-su Zhen, Rui-Juan Gao, Qing-Fang Miao. h3B7A-LDM, a novel anti-mesothelin antibody-drug conjugate with the potential to induce antitumor immunity, shows potent efficacy against solid tumors[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101550

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h3B7A-LDM, a novel anti-mesothelin antibody-drug conjugate with the potential to induce antitumor immunity, shows potent efficacy against solid tumors

doi: 10.1016/j.jpha.2026.101550

NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China

Funds:

This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China (Grant No.: 2021-I2M-1-026), the Beijing Natural Science Foundation, China (Grant Nos.: 7242201 and 7202133), and the National Natural Science Foundation of China (Grant No.: 82104052).

Received Date: Feb. 06, 2025
Accepted Date: Jan. 06, 2026
Rev Recd Date: Jan. 05, 2026
Available Online: Jan. 07, 2026

Abstract

Abstract

Antibody-drug conjugates (ADCs) are a promising class of cancer therapeutics that enable the targeted delivery of highly cytotoxic payloads to cancer cells. Mesothelin (MSLN) is an attractive therapeutic target in cancer treatment. Lidamycin (LDM), an enediyne-containing antibiotic with potent antitumor effects, has potential as ADC payload. To generate an ADC targeting MSLN, we first produced a novel anti-MSLN antibody, 3B7A, using hybridoma technology. We then obtained the humanized version, h3B7A via complementarity-determining region (CDR) grafting. This was followed by fusion with lidamycin through genetic recombination and molecular assembly to create the ADC h3B7A-LDM. h3B7A-LDM undergoes efficient internalization and lysosomal trafficking in MSLN-positive cancer cells. It demonstrates strong tumor-targeting capability and long-term persistence in tumor-bearing mice. In vitro, it exhibits potent antitumor effects, suppressing the proliferation and migration of cancer cells with sub-nanomolar half maximal inhibitory concentration (IC₅₀) values. Mechanistically, h3B7A-LDM induces cell cycle arrest and apoptosis, triggers immunogenic cell death (ICD), may elicit antitumor immunity. In vivo, h3B7A-LDM significantly inhibits tumor growth in multiple cancer xenograft models. Together, these findings support h3B7A-LDM as a promising drug candidate for treating MSLN-positive cancer.
- Mesothelin,
- Lidamycin,
- Antibody-drug conjugate,
- Antitumor activity

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References(49)

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