Disitamab vedotin: a novel antibody-drug conjugates for cancer therapy

Drug Deliv. 2022 Dec;29(1):1335-1344. doi: 10.1080/10717544.2022.2069883.

Abstract

Human epidermal growth factor receptor 2 (HER2) regulates cell mitosis, proliferation, and apoptosis. Trastuzumab is a HER2-targeted monoclonal antibody (mAB), which can prolong the overall survival rate of patients with HER2 overexpression in later periods of gastric cancer and breast cancer. Although anti-HER2 monoclonal antibody has a curative effect, adjuvant chemotherapy is still necessary to upgrade the curative effect maximumly. Antibody-drug conjugate (ADC) is a kind of therapeutic drug that contains antigen-specific antibody and cytotoxic payload, which can improve the survival time of tumor patients. To date, there are several HER2-ADC products on the market, for which two anti-HER2 ADC (trastuzumab emtansine and trastuzumab deruxtecan) have been authorized by the FDA for distinct types of HER2-positive carcinoma in the breast. Disitamab vedotin (RC48) is a newly developed ADC drug targeting HER2 that is comprised of hertuzumab coupling monomethyl auristatin E (MMAE) via a cleavable linker. This paper aims to offer a general insight and summary of the mechanism of action and the currently completed and ongoing clinical studies of RC-48 in HER-2 positive solid tumors.

Keywords: Antibody-drug conjugates; disitamab vedotin; human epidermal growth factor receptor 2; trastuzumab deruxtecan; trastuzumab emtansine.

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Immunoconjugates* / pharmacology
  • Immunoconjugates* / therapeutic use
  • Stomach Neoplasms* / drug therapy

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunoconjugates

Grants and funding

This project was supported by the National Natural Science Foundation of China (31971248) and the Shaanxi Science and Technology Innovation Team Project (2021TD-46.