An EGF receptor-targeting amphinase recombinant protein mediates anti-tumor activity in vitro and in vivo.
Acta Biochim Biophys Sin (Shanghai)
; 50(4): 391-398, 2018 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-29566107
ABSTRACT
Utilizing cytotoxic proteins linked to tumor targeting molecules as anti-tumor drugs is a promising approach. However, most cytotoxins derived from bacteria or plants have inherent problems such as large molecular weights and they trigger a strong immune system reaction, which leads to drug failure and serious side effects. Amphinase (Amph) is a ribonuclease with a low molecular weight that is found in northern leopard frog oocytes. It has strong cytotoxicity against tumor cell lines in vitro and weak immunogenicity in vivo, and is a promising candidate in the development of targeted drugs. Transforming growth factor-α (TGF-α) that binds to the epidermal growth factor receptor (EGFR) is being used as a targeting molecule for the treatment of EGFR high-expressing tumors. In this study, we expressed and purified a recombinant amphinase and its TGF-α fusion protein (AGT) separately from Escherichia coli. AGT exhibited more significant cytotoxicity in vitro on EGFR high-expressing tumor cell lines, and stronger anti-tumor effects in vivo. This fusion protein also exhibited unusual thermostability, low in vivo immunogenicity, and side effects. Our results provide a new entry point for the development of novel, highly efficient anti-tumor targeting biological agents with low immunogenicity.
Full text:
1
Database:
MEDLINE
Main subject:
Ribonucleases
/
ErbB Receptors
/
Antineoplastic Agents
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Acta Biochim Biophys Sin (Shanghai)
Journal subject:
BIOFISICA
/
BIOQUIMICA
Year:
2018
Type:
Article
Affiliation country:
China