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  3. A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

  • Cell Rep Med. 2026 Apr 21;7(4):102688. doi: 10.1016/j.xcrm.2026.102688.
Wenjing Ning 1,  Han Liu 1,  Hongye Zeng 1,  Xiaojing Qin 1,  Lin Xu 1,  Shiting Yang 1,  Yue Wang 1,  Fentian Chen 1,  Na Yuan 1,  Xiaoqing Chen 1,  Tao Xu 1,  Kexin Wu 1,  Peng Wang 1,  Chao Liu 2,  Yuanzhi Chen 3,  Ningshao Xia 4,  Xue Liu 5,  Wenxin Luo 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen 361102, China.
  • 2 State Key Laboratory of Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
  • 3 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: [email protected].
PMID: 41856115 DOI: 10.1016/j.xcrm.2026.102688
Abstract

Pancreatic Cancer remains highly lethal with limited treatment options. Although antibody-drug conjugates (ADCs) have emerged as promising therapeutic agents, their efficacy is often limited by heterogeneous antigen expression and poor tumor penetration. To address these limitations, we develop B6ADC, a nanobody-based bispecific ADC that simultaneously targets TROP2 and c-Met. In preclinical studies, B6ADC exhibits potent cytotoxicity in vitro across various TROP2/c-Met-expressing Cancer cell lines and superior tumor inhibition in vivo compared with single-target ADC combination, including the clinically approved TROP2 ADC sacituzumab govitecan and c-Met ADC Teliso-V, as well as their combination. Notably, B6ADC eradicates giant tumors with a single dose at a low concentration of 2.2 mg/kg. We present a nanobody-based BsADC that simultaneously targets TROP2 and c-Met, with broad-spectrum antitumor activity, and improves selectivity for tumors with dual-positive or weakly positive antigen expression, offering a promising strategy for treating pancreatic Cancer and other TROP2/c-Met-expressing malignancies.

Keywords

BsADC; TROP2; c-Met; nanobody-drug conjugate; pancreatic cancer.

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