Abstract
Tumor-targeted delivery of cytotoxins presents considerable advantages over their passive transport. Chemical conjugation of cytotoxic module to antibody is limited due to insufficient reproducibility of synthesis, and recombinant immunotoxins are aimed to overcome this disadvantage. We obtained genetically encoded immunophotosensitizer 4D5scFv-miniSOG and evaluated its photocytotoxic effect in vitro. A single-chain variable fragment (scFv) of humanized 4D5 antibody was used as a targeting vehicle for selective recognition of the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) overexpressed in many human carcinomas. As a phototoxic module we used a recently described photoactivated fluorescent flavoprotein miniSOG. We found that recombinant protein 4D5scFv-miniSOG exerts a highly specific photo-induced cytotoxic effect on HER2/neu-positive human breast adenocarcinoma SK-BR-3 cells (IC50= 160 nM). We demonstrated that the 4D5scFv-miniSOG specifically binds to HER2-positive cells and internalizes via receptor-mediated endocytosis. Co-treatment of breast cancer cells with 4D5scFv-miniSOG and Taxol or junction opener protein JO-1 produced remarkable additive effects.
| Original language | English |
|---|---|
| Pages (from-to) | 831-840 |
| Number of pages | 10 |
| Journal | Theranostics |
| Volume | 3 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2013 |
| Externally published | Yes |
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Keywords
- HER2/neu
- Immunophototoxin
- Phototoxicity
- Single-chain variable fragment.
- Tumor-targeted delivery
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Cite this
Genetically encoded immunophotosensitizer 4D5scFv-miniSOG is a highly selective agent for targeted photokilling of tumor cells in vitro. / Mironova, Kristina E.; Proshkina, Galina M.; Ryabova, Anastasiya V.; Stremovskiy, Oleg A.; Lukyanov, Sergey A.; Petrov, Rem V.; Deyev, Sergey M.
In: Theranostics, Vol. 3, No. 11, 2013, p. 831-840.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetically encoded immunophotosensitizer 4D5scFv-miniSOG is a highly selective agent for targeted photokilling of tumor cells in vitro
AU - Mironova, Kristina E.
AU - Proshkina, Galina M.
AU - Ryabova, Anastasiya V.
AU - Stremovskiy, Oleg A.
AU - Lukyanov, Sergey A.
AU - Petrov, Rem V.
AU - Deyev, Sergey M.
PY - 2013
Y1 - 2013
N2 - Tumor-targeted delivery of cytotoxins presents considerable advantages over their passive transport. Chemical conjugation of cytotoxic module to antibody is limited due to insufficient reproducibility of synthesis, and recombinant immunotoxins are aimed to overcome this disadvantage. We obtained genetically encoded immunophotosensitizer 4D5scFv-miniSOG and evaluated its photocytotoxic effect in vitro. A single-chain variable fragment (scFv) of humanized 4D5 antibody was used as a targeting vehicle for selective recognition of the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) overexpressed in many human carcinomas. As a phototoxic module we used a recently described photoactivated fluorescent flavoprotein miniSOG. We found that recombinant protein 4D5scFv-miniSOG exerts a highly specific photo-induced cytotoxic effect on HER2/neu-positive human breast adenocarcinoma SK-BR-3 cells (IC50= 160 nM). We demonstrated that the 4D5scFv-miniSOG specifically binds to HER2-positive cells and internalizes via receptor-mediated endocytosis. Co-treatment of breast cancer cells with 4D5scFv-miniSOG and Taxol or junction opener protein JO-1 produced remarkable additive effects.
AB - Tumor-targeted delivery of cytotoxins presents considerable advantages over their passive transport. Chemical conjugation of cytotoxic module to antibody is limited due to insufficient reproducibility of synthesis, and recombinant immunotoxins are aimed to overcome this disadvantage. We obtained genetically encoded immunophotosensitizer 4D5scFv-miniSOG and evaluated its photocytotoxic effect in vitro. A single-chain variable fragment (scFv) of humanized 4D5 antibody was used as a targeting vehicle for selective recognition of the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) overexpressed in many human carcinomas. As a phototoxic module we used a recently described photoactivated fluorescent flavoprotein miniSOG. We found that recombinant protein 4D5scFv-miniSOG exerts a highly specific photo-induced cytotoxic effect on HER2/neu-positive human breast adenocarcinoma SK-BR-3 cells (IC50= 160 nM). We demonstrated that the 4D5scFv-miniSOG specifically binds to HER2-positive cells and internalizes via receptor-mediated endocytosis. Co-treatment of breast cancer cells with 4D5scFv-miniSOG and Taxol or junction opener protein JO-1 produced remarkable additive effects.
KW - HER2/neu
KW - Immunophototoxin
KW - Phototoxicity
KW - Single-chain variable fragment.
KW - Tumor-targeted delivery
UR - http://www.scopus.com/inward/record.url?scp=84888797993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888797993&partnerID=8YFLogxK
U2 - 10.7150/thno.6715
DO - 10.7150/thno.6715
M3 - Article
AN - SCOPUS:84888797993
VL - 3
SP - 831
EP - 840
JO - Theranostics
JF - Theranostics
SN - 1838-7640
IS - 11
ER -