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Disitamab Vedotin is mainly used to treat patients with locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) with HER2 overexpression who have received at least two systemic chemotherapy regimens. It was first approved in China, providing a new treatment option for patients with HER2-positive gastric cancer who are resistant or intolerant to existing treatment options.

Disitamab vedotin (RC48) is an antibody-drug conjugate (ADC) comprising a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) conjugated via a cleavable linker to the cytotoxic agent Monomethyl auristatin E (MMAE). Disitamab vedotin enhances antitumor immunity[1].

Disitamab Vedotin is an antibody-drug conjugate (ADC) consisting of the human epidermal growth factor receptor 2 (HER2)-specific antibody hertuzumab (disitamab) connected to the cytotoxic monomer monomethyl auristatin E (MMAE) through a cleavable valine-citrulline-para-aminobenzoic acid alanine carbonate (mc-Val-Cit-PABC) linker. This design enables disitamab vedotin to specifically target HER2-overexpressing cancer cells and release MMAE after entering the cells through internalization, inducing cell apoptosis.

Disitamab Vedotin is produced by conjugating the antibody hertuzumab to mc-Val-Cit-PABC-MMAE (29.3). General methods for such conjugation have been provided in the patent literature and begin with the partial reduction of the disulfide bonds present in the hertuzumab antibody. This is accomplished by treating the antibody with tris(2-carboxyethyl)phosphine (TCEP) and bisethylenediaminepentaacetic acid (DTPA) in phosphate buffered saline (PBS) to produce 29.2. The sulfhydryl groups present in 29.2 react with a dimethyl sulfoxide (DMSO) solution of 29.3 to obtain Disitamab Vedotin.

HER2

[1] Deeks ED. Disitamab Vedotin: First Approval. Drugs. 2021;81(16):1929-1935. DOI:10.1007/s40265-021-01614-x
[2] Jiang J, et al. Preclinical safety profile of disitamab vedotin: a novel anti-HER2 antibody conjugated with MMAE. Toxicol Lett. 2020;324:30-37. DOI:10.1016/j.toxlet.2019.12.027
[3] Huang L, Wang R, Xie K, et al. A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+?tumors in hPD-1 transgenic mouse model and contributes immune memory formation. Breast Cancer Res Treat. 2022;191(1):51-61. DOI:10.1007/s10549-021-06384-4