title: Antibody-based targeting of CD24 enhances antitumor effect of cetuximab via attenuating phosphorylation of Src/STAT3.
abstract: Epidermal growth factor receptor (EGFR) is a cell-surface receptor for some extracellular protein ligands relating to cancers and has been recognized as a key target for tumor therapy. Cetuximab, a chimerical monoclonal EGFR IgG1 antibody, is used for the treatment of various malignancies. However, recent clinical trials reported that the anti-tumor effect of cetuximab is still controversial. Cluster of differentiation 24 (CD24) is a tumor-associated antigen correlating with poor prognosis and regulating the activity of Src/STAT3 in multiple cancers. G7mAb was an anti-CD24 antibody derived by hybridoma technology in our previous study. To further evaluate the relationship between cetuximab and G7mAb in cancer therapy, this combination treatment was performed in vitro (A549, HT-29 and Huh-7 cells) and in vivo (xenograft mouse models). We showed that G7mAb suppressed the invasion and enhanced the anti-proliferation effect of cetuximab in A549, HT-29 and Huh-7 cells. Combination of cetuximab with G7mAb had enhanced effects on blocking the activation of signal transducer and activator of transcription 3 (STAT3) signal pathway. Furthermore, combination therapy of cetuximab with G7mAb significantly suppressed tumor developments and improved the survival rates in xenografted mice. In conclusion, G7mAb enhanced the antitumor effect of cetuximab by attenuating phosphorylation of Src/STAT3 both in vitro and in vivo. Combination of antibodies targeting EGFR or CD24 provided a potential strategy for cancer therapy.
authors.affiliation: State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China. Electronic address: minwang@cpu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China. Electronic address: juancpu@126.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051927:CD24 Antigen / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051927:CD24 Antigen; C497889:CD24 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D066246:ErbB Receptors; D019061:src-Family Kinases; D000068818:Cetuximab
keywords: Antibody; CD24; Combined therapeutic; EGFR; Neoplasm; STAT3