title: A recombinant scFv-FasLext as a targeting cytotoxic agent against human Jurkat-Ras cancer.
abstract: BACKGROUND
  Targeted 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).
  
  
  RESULTS
  The cc49scFv-FasLext is highly effective in in vitro killing 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-FasLext only increased cytotoxicity 500-fold as compared with sFasL against TAL6+ HeLa cells in in vitro assays. The high specificity and strong cytotoxicity of cc49scFv-FasLext made it feasible to cure IP-implanted Jurkat-Ras tumors in SCID mice.
  
  
  CONCLUSIONS
  Our study demonstrated that scFv-FasLext with a strong cytotoxicity against sensitive human tumor targets may be useful as effective chemotherapeutic agents.
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Derek V
authors.initials: DV
authors.lastname: Chan
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Chiao-Ying A
authors.initials: CY
authors.lastname: Ju
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roffler
authors.forename: Shyr-Te
authors.initials: ST
authors.lastname: Ju
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000235:genetics* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D019169:Jurkat Cells; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D057127:Single-Chain Antibodies / Q000235:genetics* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D007128:Immunoglobulin Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C505661:FASLG protein, human