Induction of Tumor Cell Apoptosis by TRAIL Gene Therapy
Members of the tumor necrosis factor (TNF) superfamily influence a variety of immunological functions, including cellular activation, proliferation, and death, upon interaction with a corresponding superfamily of receptors. Whereas interest in the apoptosis-inducing molecules TNF and Fas ligand has peaked because of their participation in events such as autoimmune disorders, activation-induced cell death, immune privilege, and tumor evasion from the immune system, another death-inducing family member, TNF-related apoptosis-inducing ligand (TRAIL), or Apo-2 ligand, has generated excitement because of its unique ability to induce apoptosis in a wide range of transformed cell lines but not in normal tissues. TRAIL is well tolerated when given to healthy animals, and no observable histological or functional changes have been observed in any of the tissues or organs examined. Moreover, multiple injections of soluble TRAIL into mice beginning the day after tumor implantation can significantly suppress the growth of the tumors, with many animals becoming tumor-free. One potential drawback to these findings is that large amounts of soluble TRAIL may be required to inhibit tumor formation, possibly because of the pharmacokinetic profile of soluble TRAIL that indicates that, after intravenous injection, the majority of the protein is rapidly cleared. Increasing the in vivo half-life of recombinant soluble TRAIL or developing an alternative means of delivery may increase the relative tumoricidal activity of TRAIL such that larger, more established tumors could be eradicated as efficiently as smaller tumors. The information presented here describes the production of an adenoviral vector engineered to carry the complementary DNA (cDNA) for murine TRAIL (hTRAIL).
- Treatment Strategies in Metastatic Renal Cell Carcinoma: Cytokines, Vaccines, and Gene Therapy
- Hormonal and Differentiation Agents in Cancer Growth Suppression
- cDNA Microarray and Bioinformatic Analysis of Nuclear Factor-B Related Genes in Squamous Cell Carcinoma
- Detection of Telomerase hTERT Gene Expression and Its Splice Variants by RT-PCR
- Chemosensitivity Testing Using Microplate Adenosine Triphosphate-Based Luminescence Measurements
- Proteolytic Systems: Constructing Degradomes
- 测定细胞内钙离子浓度的方法
- 真核细胞表达的转录水平调控
- 细胞因子的检测方法
- Enhanced Permeability and Retention (EPR) Effect for Anticancer Nanomedicine Drug Targeting