Abstract | BACKGROUND: OBJECTIVE AND METHODS: To improve efficacy and minimize toxicity of EGFR inhibition treatment, we re-engineered cetuximab by humanizing its Fab regions and minimizing its glycan contents to generate HLX07. RESULTS:
HLX07 binds to EGFR with similar affinity as cetuximab and shows better bioactivity compared to cetuximab in vitro. In vivo studies demonstrated that HLX07 significantly inhibited the growth of A431, FaDu, NCI-H292, and WiDr tumor cells and synergized them with chemotherapeutics and immune simulator agents such as anti-PD-1. In cynomolgus monkeys, 13-week repeat-dose GLP toxicokinetic studies showed minimal-to-mild toxicities in the dose range of up to 60 mg/kg/wk. In the preliminary phase 1 dose-escalation study, HLX07 had showed lower incidence of skin rashes with grade >2 severities. CONCLUSION:
HLX07 is currently under phase 1/2 clinical development. We believe HLX07 would potentially be an alternative for patients who have been suffering from cetuximab-mediated toxicity.
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Authors | Pei-Hua Lin, Chi-Ling Tseng, Yun-Chih Cheng, Chieh-Hsin Ho, Shih Chieh Chen, Yanling Wang, Eugene Liu, Hassan Issafras, Weidong Jiang |
Journal | Expert opinion on biological therapy
(Expert Opin Biol Ther)
Vol. 21
Issue 11
Pg. 1491-1507
(11 2021)
ISSN: 1744-7682 [Electronic] England |
PMID | 34632911
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- ErbB Receptors
- Cetuximab
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Topics |
- Antibodies, Monoclonal
- Antineoplastic Agents
(adverse effects)
- Cell Line, Tumor
- Cetuximab
- ErbB Receptors
- Head and Neck Neoplasms
- Humans
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