A single-chain variable fragment-anticancer lytic peptide (scFv-ACLP) fusion protein for targeted cancer treatment.
Rui ZhangPengfei PeiYifan WangQuanqiang GuoShi-Zhong LuoLong ChenPublished in: Chemical biology & drug design (2023)
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 (G 4 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.
Keyphrases
- locally advanced
- epidermal growth factor receptor
- rectal cancer
- tyrosine kinase
- squamous cell carcinoma
- cancer therapy
- advanced non small cell lung cancer
- small cell lung cancer
- drug delivery
- amino acid
- drug induced
- papillary thyroid
- climate change
- emergency department
- pseudomonas aeruginosa
- lymph node metastasis
- cystic fibrosis
- transcription factor
- protein protein
- cell free