P-014 - A Tumor-penetrating Recombinant Protein anti-EGFR-iRGD Enhance Efficacy of Paclitaxel in 3D multicellular spheroids and Gastric Cancer in vivo

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Basic Science
Gastric Cancer
Presenter H. Sha
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors H. Sha, Z. Zou, B. Liu
  • Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing/CN

Abstract

Introduction

Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. Chemotherapy employing paclitaxel (PTX) is widely used for treating various kinds of cancer including gastric cancer.

Methods

Recombinant protein anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability were expressed in E. coli BL21 (DE3) and purified by nickel-nitrilotriacetic acid affinity chromatography. We use tumor cell lines (2D), multicellular spheroids (3D), and mice to analyze the antitumor activity of recombinant protein. To investigate the ability of anti-EGFR-iRGD to improve other drugs (e.g. PTX) penetrating into tumor, we used multicellular spheroids and mice.

Results

We have successfully constructed a recombinant protein named anti-EGFR-iRGD, a dual target of EGFR and integrin and high permeable protein. It could spread extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines (2D), multicellular spheroids (3D), and mice. Moreover, we demonstrated the therapeutic efficacy of PTX combined with anti-EGFR-iRGD on monolayer cells (2D), multicellular spheroids (3D) and tumor-bearing mice for the first time.

Conclusion

Our results provide impetus for further studies for potentially using iRGD based fusion protein anti-EGFR-iRGD with standard cytotoxic treatment regimens for enhancing therapy of gastric cancer patients.

Figure: P-014