Disitamab vedotin: a novel antibody-drug conjugates for cancer therapy
Fan Shi1, Yanli Liu1, Xuexiao Zhou2
1State Key Laboratory of Military Stomatology, Department of General Dentistry and Emergency, School of Stomatology, Air Force Military Medical University, Xi'an, China.
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.
Insights
Disitamab vedotin (RC48) is a novel antibody-drug conjugate targeting HER2-positive solid tumors. This review summarizes RC48
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Human epidermal growth factor receptor 2 (HER2) is a key regulator of cell growth and is overexpressed in several cancers.
- Trastuzumab, a HER2-targeted monoclonal antibody (mAB), improves survival in HER2-positive cancers but often requires adjuvant therapy.
- Antibody-drug conjugates (ADCs) combine targeted antibody delivery with cytotoxic payloads to enhance anti-tumor efficacy.
Purpose of the Study:
- To provide an overview of the mechanism of action of Disitamab vedotin (RC48).
- To summarize completed and ongoing clinical studies of RC-48 in HER2-positive solid tumors.
- To highlight RC48 as a promising therapeutic agent in HER2-targeted cancer therapy.
Main Methods:
- Review of preclinical data and clinical trial results for Disitamab vedotin (RC48).
- Analysis of RC48's mechanism, including its antibody component (hertuzumab) and cytotoxic payload (MMAE).
- Examination of clinical efficacy and safety data from ongoing and completed studies.
Main Results:
- Disitamab vedotin (RC48) demonstrates potent anti-tumor activity in preclinical models of HER2-positive solid tumors.
- Clinical trials indicate promising efficacy and a manageable safety profile for RC48 in patients with HER2-positive cancers.
- RC48 utilizes a cleavable linker to deliver the cytotoxic agent MMAE specifically to HER2-expressing tumor cells.
Conclusions:
- Disitamab vedotin (RC48) represents a significant advancement in HER2-targeted therapy.
- RC48 shows potential as a valuable treatment option for patients with various HER2-positive solid tumors.
- Further clinical evaluation of RC48 is warranted to establish its full therapeutic potential.
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