title: Tumor-penetration and antitumor efficacy of cetuximab are enhanced by co-administered iRGD in a murine model of human NSCLC.
abstract: Lung cancer is the leading cause of cancer-associated mortality, worldwide. For this reason, novel therapies are required for the treatment of this devastating disease. Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR), which is overexpressed in a variety of solid tumors, including non-small cell lung cancer (NSCLC). The therapeutic efficacy of cetuximab for NSCLC is limited to use as a monotherapy or in combination with chemotherapy. The objective of the present study was to develop a novel strategy to enhance the therapeutic efficacy of cetuximab for NSCLC by a co-administration with the tumor-penetrating internalizing RGD peptide (iRGD). Human NSCLC subcutaneous xenograft models established with the A549 cell line in nude mice were treated with 30 mg/kg cetuximab, 4 mg/kg iRGD, cetuximab plus iRGD or phosphate-buffered saline. The tumor-penetration,in vivotherapeutic efficacy and involved mechanism were evaluated. The present study showed that the A549 xenograft model is sensitive to the co-administration of cetuximab and iRGD. Treatment with cetuximab plus iRGD resulted in a significant increase in the tumor-penetration of cetuximab and tumor reduction compared with cetuximab monotherapy. In conclusion, iRGD enhances the effects of co-administered cetuximab in an NSCLC model. The combined application of cetuximab and iRGD may be a novel strategy to enhance the clinical therapeutic efficacy of cetuximab for the treatment of NSCLC.
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China; Department of Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Oncology, Xuzhou Tumor Hospital, Xuzhou, Jiangsu 221005, P.R. China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Ding
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Liantao
authors.initials: L
authors.lastname: Li
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
keywords: cetuximab; combination therapy; internalizing RGD peptide; non-small cell lung cancer; tumor-penetrating peptide