A single-chain variable fragment-anticancer lytic peptide (scFv-ACLP) fusion protein for targeted cancer treatment

Chem Biol Drug Des. 2023 Jun;101(6):1406-1415. doi: 10.1111/cbdd.14223. Epub 2023 Mar 14.

Abstract

Antibody-directed drugs for targeted cancer treatment have become a hot topic in new anticancer drug development; however, antibody-fused therapeutic peptides were rarely documented. Herein, we designed a fusion protein with a cetuximab-derived single-chain variable fragment targeting epidermal growth factor receptor (anti-EGFR scFv) and the anticancer lytic peptide (ACLP) ZXR2, connected by a linker (G4 S)3 and MMP2 cleavage site. The anti-EGFR scFv-ZXR2 recombinant protein showed specific anticancer activity on EGFR-overexpressed cancer cell lines in a concentration- and time-dependent manner, as it can bind to EGFR on cancer cell surfaces. This fusion protein caused cell membrane lysis as ZXR2, and showed improved stability in serum compared with ZXR2. These results suggest that scFv-ACLP fusion proteins may be potential anticancer drug candidates for targeted cancer treatment, which also provide a feasible idea for targeted drug design.

Keywords: EGFR; anticancer peptide; cancer treatment; scFv; targeted delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cetuximab / therapeutic use
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Single-Chain Antibodies* / pharmacology
  • Single-Chain Antibodies* / therapeutic use

Substances

  • Antineoplastic Agents
  • Cetuximab
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Single-Chain Antibodies
  • peptide ZXR2