title: Genetically encoded immunophotosensitizer 4D5scFv-miniSOG is a highly selective agent for targeted photokilling of tumor cells in vitro.
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.
authors: 1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya, 16/10, Moscow, 117997, Russia;
authors: Kristina E
authors: KE
authors: Mironova
authors: Galina M
authors: GM
authors: Proshkina
authors: Anastasiya V
authors: AV
authors: Ryabova
authors: Oleg A
authors: OA
authors: Stremovskiy
authors: Sergey A
authors: SA
authors: Lukyanov
authors: Rem V
authors: RV
authors: Petrov
authors: Sergey M
authors: SM
authors: Deyev
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005420:Flavoproteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000235:genetics / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005420:Flavoproteins; D000922:Immunotoxins; D008164:Luminescent Proteins; D017319:Photosensitizing Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C000603949:4D5scFv-miniSOG immunophototoxin; C508053:ERBB2 protein, human
keywords: HER2/neu; immunophototoxin; phototoxicity; single-chain variable fragment.; tumor-targeted delivery