A recombinant scFv-FasLext as a targeting cytotoxic agent against human Jurkat-Ras cancer
Copyright policy )A recombinant scFv-FasLext as a targeting cytotoxic agent against human Jurkat-Ras cancer
AbstractBackgroundTargeted therapy of human cancers is an attractive approach and has been investigated with limited success. We have developed novel cytotoxic agents for targeted therapy of human cancers based on the extracellular cytotoxicity domain of CD178 (FasL) and the specificity offered by single chain antibodies (scFv) against dominant human tumor Ag TAG-72 (cc49scFv) and TAL6 (L6scFv).ResultsThe cc49scFv-FasLextis highly effective inin vitrokilling of human TAG-72+Jurkat-Ras tumor cells with a 30,000 fold greater cytotoxicity as compared to soluble FasL (sFasL). On the other hand, L6scFv-FasLextonly increased cytotoxicity 500-fold as compared with sFasL against TAL6+HeLa cells inin vitroassays. The high specificity and strong cytotoxicity of cc49scFv-FasLextmade it feasible to cure IP-implanted Jurkat-Ras tumors in SCID mice.ConclusionOur study demonstrated that scFv-FasLextwith a strong cytotoxicity against sensitive human tumor targets may be useful as effective chemotherapeutic agents.
- Boston College United States
- Boston University United States
- University of Virginia United States
- Boston University School of Medicine / Department of Medicine United States
- The Ohio State University United States
Biochemistry, medical, Fas Ligand Protein, Receptor, ErbB-2, Endocrinology, Diabetes and Metabolism, Research, Recombinant Fusion Proteins, Clinical Biochemistry, Antineoplastic Agents, Cell Biology, Mice, SCID, Xenograft Model Antitumor Assays, Jurkat Cells, Mice, Neoplasms, Animals, Humans, Pharmacology (medical), Molecular Biology, Immunoglobulin Fragments, HeLa Cells, Single-Chain Antibodies
Biochemistry, medical, Fas Ligand Protein, Receptor, ErbB-2, Endocrinology, Diabetes and Metabolism, Research, Recombinant Fusion Proteins, Clinical Biochemistry, Antineoplastic Agents, Cell Biology, Mice, SCID, Xenograft Model Antitumor Assays, Jurkat Cells, Mice, Neoplasms, Animals, Humans, Pharmacology (medical), Molecular Biology, Immunoglobulin Fragments, HeLa Cells, Single-Chain Antibodies
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