Accession Number : ADA407205


Title :   TRAIL-Based Anticancer Drug Development


Descriptive Note : Final rept. 15 Jun 2001-14 Jun 2002


Corporate Author : PITTSBURGH UNIV PA


Personal Author(s) : Seol, Dai-Wu


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a407205.pdf


Report Date : Jul 2002


Pagination or Media Count : 104


Abstract : The specific aim of the funded research was to develop a TRAIL-based anticancer drug using a gene therapy approach. To accomplish the proposed aim, I have created a novel TRAIL gene composed of three functional elements (secretion signal, trimer-forming domain, and TRAIL gene segment for apoptosis induction), and a naked DNA- type delivery vector. Functional analysis revealed that this novel artificial gene expresses and secrets into the culture supernatant, and efficiently kills various tumor cells but not normal cells tested. Recombinant TRAIL protein was observed to be more potent in target cell killing when combined with other potentiators such as Actinomycin D, Interferon-gamma, and Akt inhibitors. Thus, novel TRAIL gene-based therapy in combination with these potentiators is expected to produce better therapeutic efficacy. Currently, developed gene therapy tool is tested in animal tumor models. If proven to be safe and effective in vivo, this novel gene therapy approach will be tested for human cancers. Successful completion of the current research project will provide a powerful therapeutic tool for treatment of human cancers.


Descriptors :   *APOPTOSIS , *BREAST CANCER , *DEOXYRIBONUCLEIC ACIDS , *DRUGS , CELLS(BIOLOGY) , DELIVERY , FUNCTIONAL ANALYSIS , GENE THERAPY , HUMANS , LABORATORY ANIMALS , NEOPLASMS , PROTEINS , SECRETION , SIGNALS , TOOLS


Subject Categories : Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE