Strategies for the enhancement of anti-cancer effect of phosphodiesterase type 5 inhibitors using drug binding fusion proteins

• Published in: Biotechnology and bioprocess engineering Vol. 29; no. 1; pp. 85 - 96
• Main Authors: Kim, Hongbin, Keum, Chang Yeop, Lim, Su Yeon, Lim, Kwang Suk
• Format: Journal Article
• Language: English
• Published: Seoul The Korean Society for Biotechnology and Bioengineering 01.02.2024; Springer Nature B.V; 한국생물공학회
• Subjects: Antibodies; Anticancer properties; antineoplastic activity; Antineoplastic drugs; Binding; Biotechnology; Cancer; Chemistry; Chemistry and Materials Science; domain; drugs; ErbB-2 protein; Erectile dysfunction; Fusion protein; Industrial and Production Engineering; Inhibitors; Pharmacology; Phosphodiesterase; Proteins; recombinant fusion proteins; Research Paper; therapeutics; 생물공학; PDE5 inhibitors; HER2; Targeted delivery; Recombinant fusion proteins; Self-assemble
• ISSN: 1226-8372; 1976-3816
• DOI: 10.1007/s12257-024-00014-8

Drug repurposing is a rapidly growing for the development of new therapeutic agents. Among them, phosphodiesterase-5 (PDE5) inhibitors, which show excellent effects as a treatment for erectile dysfunction, have been continuously reported for their potential as anti-cancer agents. It is necessary to apply targeted delivery systems to enhance the efficacy of the PDE5 inhibitors (PDE5i) as anti-cancer drugs. In this study, PDE5 inhibitor-binding domain (PBD) was developed to incorporate PDE5i into antibody using biological affinity binding without any chemical modifications. The PBD spontaneously bound with PDE5i, resulting in the formation of PBD/PDE5i complex. We also constructed a recombinant fusion protein composed of an anti-HER2 scFv and PBD (HER2 scFv-PBD) to deliver the PDE5i for the treatment of HER2 positive cancer cells. HER2 scFv-PBD could deliver the PDE5i into HER2-positive cancer cells and enhanced anti-cancer effect of the PDE5i. We have demonstrated the potential of tumor-directed PDE5 inhibition as a novel form of targeted therapy using drug binding fusion proteins.