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引用次数: 0
摘要
抗体-药物共轭物(ADC)已成为一类新型的癌症靶向疗法,并已成功应用于乳腺癌(BC)的治疗。盘状蛋白结构域受体 1(DDR1)是一种单跨膜受体酪氨酸激酶,已被确定为可能的癌症靶点。在这项研究中,我们探索了一种名为 T4H11-DM4 的抗 DDR1 ADC 治疗 DDR1 阳性 BC 的潜力。我们证实,在 BC 组织中,DDR1 蛋白表达和 RNA 表达均很高。在体外,T4H11-DM4对表达DDR1的BC细胞具有强效细胞毒性,IC50在纳摩尔范围内。在小鼠BC异种移植模型中,T4H11-DM4能显著消除BC肿瘤,且无明显毒性。综上所述,我们的研究结果表明,DDR1 可以作为一种很有前景的治疗靶点用于治疗 BC。
Antibody-drug conjugates targeting DDR1 as a novel strategy for treatment of breast cancer.
Antibody-drug conjugates (ADCs) have emerged as a novel class of targeted cancer therapies and been successfully applied in the treatment of breast cancer (BC). Discoidin domain receptor 1 (DDR1) is a single transmembrane receptor tyrosine kinase and has been identified as a possible target for cancer. In this study, we explored the potential of an anti-DDR1 ADC, named T4H11-DM4, for the treatment of DDR1-positive BC. We demonstrated that high protein expression and RNA expression of DDR1 in BC tissues. In vitro, T4H11-DM4 was potently cytotoxic to DDR1-expressing BC cells, with IC50 in the nanomolar range. In mice BC xenograft models, T4H11-DM4 dramatically eliminated BC tumours, without observable toxicity. Taken together, our findings demonstrated that DDR1 can serve as a promising therapeutic target for BC.
期刊介绍:
Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs.
Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.