β-Diketone modified trastuzumab: A next-generation of Herceptin for resistant breast cancer cells?

Lu, Jianguo; Pu, Jun; Lü, Xin; Fu, Haiyan; Wei, Mengying; Yang, Guodong

doi:10.1016/j.mehy.2012.07.030

Cited by 1 publication

(1 citation statement)

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“…According to a previous study, deficiency in the ADCC effect of trastuzumab in breast cancer patients was directly associated with trastuzumab resistance. 43 All these data indicate that hertuzumab is an anti-HER2 antibody with high affinity and effective functions.…”

Section: Discussionmentioning

confidence: 92%

An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer

Yu²,

Jiang

et al. 2016

Cancer Biology & Therapy

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Antibody-drug conjugate (ADC) is a novel class of therapeutics for cancer target therapy. This study assessed antitumor activity of ADC with an antimitotic agent, monomethyl auristatin E (MMAE) and a humanized monoclonal anti-HER2 antibody, hertuzumab, in gastric cancer. The efficacy of hertuzumab-MC-Val-Cit-PAB-MMAE (hertuzumab-vcMMAE) on human epidermal growth factor receptor 2 (HER2) positive human gastric cancer cells, NCI-N87, was evaluated in vitro and in vivo. The cytotoxicity of hertuzumab was significantly enhanced after conjugation with MMAE. Compared to trastuzumab, hertuzumab had a higher affinity to HER2 and had more potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro. After conjugation with MMAE, the binding specificity for HER2 was not affected. Furthermore, the internalization of hertuzumab-vcMMAE in HER2 positive gastric cancer cells was verified. Although the conjugation of hertuzumab and MMAE decreased the ADCC effect, the overall cytotoxicity was dramatically increased in HER2 positive gastric cancer cells. In vitro data on this hertuzumab-vcMMAE has exerted much stronger antitumor activity compared to trastuzumab-DM1 in HER2 positive gastric cancer cells. A single administration of hertuzumab-vcMMAE at 5 or 10 mg/kg showed high potency and a sustained tumor inhibitory effect on NCI-N87 xenografts in mice. In conclusion, hertuzumab-vcMMAE conjugate is a highly effective anti-HER2 targeted therapy for HER2-positive gastric cancer.

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Section: Discussionmentioning

confidence: 92%