Chemotherapy-induced peripheral neuropathy(CIPN)is one of the pervasive side effects of chemotherapy,leading to poor quality of life in cancer patients.Discovery of powerful analgesics for CIPN is an urgent and substantial clinical need.Nerve growth factor(NGF),a classic neurotrophic factor,has been identified as a potential therapeutic target for pain.In this study,we generated a humanized NGF monoclonal antibody(DS002)that most effectively blocked the interaction between NGF and tropomyosin receptor kinase A(TrkA).We showed that DS002 blocked NGF binding to TrkA in a dose-dependent manner with an IC50 value of 6.6 nM;DS002 dose-dependently inhibited the proliferation of TF-1 cells by blocking the TrkA-mediated downstream signaling pathway.Furthermore,DS002 did not display noticeable species differences in its binding and blocking abilities.In three chemotherapy-induced rat models of CIPN,subcutaneous injection of DS002 produced a significant prophylactic effect against paclitaxel-,cisplatin-and vincristine-induced peripheral neuropathy.In conclusion,we demonstrate for the first time that an NGF inhibitor effectively alleviates pain in animal models of CIPN.DS002 has the potential to treat CIPN pain in the clinic.

Zhi-juan Liang;Jie Tan;Lei Tang;Zuo-bin Xie;Gan-jun Chen;Guo-jian Liu;Lin Yuan;Kai-xin Wang;Hua-ping Ding;Hong Qiu;Qi Wang;Gui-feng Wang;Yi-li Chen;Chun-he Wang

Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China;Dartsbio Pharmaceuticals,Ltd.,Zhongshan 528400,China;Shanghai Mabstone Biotechnologies,Ltd.,Shanghai 201203,China

中国药理学报（英文版）

[1]Zhi-juan Liang;Jie Tan;Lei Tang;Zuo-bin Xie;Gan-jun Chen;Guo-jian Liu;Lin Yuan;Kai-xin Wang;Hua-ping Ding;Hong Qiu;Qi Wang;Gui-feng Wang;Yi-li Chen;Chun-he Wang-.NGF monoclonal antibody DS002 alleviates chemotherapy-induced peripheral neuropathy in rats)[J].中国药理学报（英文版）,2022(11):2841-2847

DS002

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