0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A novel bispecific antibody drug conjugate targeting HER2 and HER3 with potent therapeutic efficacy against breast cancer.

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

          Related collections

          Author and article information

          Journal
          Acta Pharmacol Sin
          Acta pharmacologica Sinica
          Springer Science and Business Media LLC
          1745-7254
          1671-4083
          Aug 2024
          : 45
          : 8
          Affiliations
          [1 ] Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
          [2 ] Jecho Institute Co., Ltd., Shanghai, 200240, China.
          [3 ] Jecho Laboratories, Inc., Frederick, MD, 21704, USA.
          [4 ] Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China. bhzhang@sjtu.edu.cn.
          [5 ] Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China. jianweiz@sjtu.edu.cn.
          [6 ] Jecho Institute Co., Ltd., Shanghai, 200240, China. jianweiz@sjtu.edu.cn.
          [7 ] Jecho Laboratories, Inc., Frederick, MD, 21704, USA. jianweiz@sjtu.edu.cn.
          Article
          10.1038/s41401-024-01279-8
          10.1038/s41401-024-01279-8
          11272928
          38605180
          36b9dae8-c5df-40b2-b744-910dd24a4d8f
          History

          target specificity,DAR,bispecific antibody drug conjugate,breast cancer,drug distribution

          Comments

          Comment on this article