Epithelial cell adhesion moleculetargeting designed ankyrin repeat proteintoxin fusion Ec1LoPE exhibits potent cytotoxic action in prostate cancer cells.
Oncol Rep
; 47(5)2022 May.
Article
in En
| MEDLINE
| ID: mdl-35315504
ABSTRACT
Targeted anticancer therapeutics offer the advantage of reducing cytotoxic side effects to normal cells by directing the cytotoxic payload selectively to cancer cells. Designed ankyrin repeat proteins (DARPins) are promising nonimmunoglobulinbased scaffold proteins for payload delivery to cancerassociated molecular targets. Epithelial cell adhesion molecule (EpCAM) is overexpressed in 4060% of prostate cancers (PCs) and is associated with metastasis, increased risk of PC recurrence and resistance to treatment. Here, we investigated the use of DARPin Ec1 for targeted delivery of Pseudomonas exotoxin A variant (LoPE) with low immunogenicity and low nonspecific toxicity to EpCAMexpressing prostate cancer cells. Ec1LoPE fusion protein was radiolabeled with tricarbonyl technetium99m and its binding specificity, binding kinetics, cellular processing, internalization and cytotoxicity were evaluated in PC3 and DU145 cell lines. Ec1LoPE showed EpCAMspecific binding to EpCAMexpressing prostate cancer cells. Rapid internalization mediated potent cytotoxic effect with picomolar IC50 values in both studied cell lines. Taken together, these data support further evaluation of Ec1LoPE in a therapeutic setting in a prostate cancer model in vivo.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Designed Ankyrin Repeat Proteins
Limits:
Humans
/
Male
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2022
Document type:
Article
Affiliation country:
Sweden