Study On Oncolytic Poxyirus Carrying TRAIL-IETD-IL24Double Genes For Cancer Target Therapy

In today’s world，more than7million people lose their lives because of cancer each year，and the number is rising rapidly. At present in our country， the number of cancer cases isincreasing year by year. Due to the limitation of various reaso ns，the traditional means of cancertreatment’s effect is not ideal. So the novel biological therapy showes a brighter prospect.“Targeting Gene-VirotherapyofCancer”， a novel strategy for cancer treatment， which isput forward by Pro. Liu， combined the advantages of gene therapy with viroherapy. The stategycombined virus multiplication in specific tomor cells with gene therapy， promotes tomorapoptosis. Enhancing the ability of virus tumor-specific multiplication and carrying standouttherapeutic genes will be the key to achieve the best therapeutic efficacy.Because of the following advantages in poxvirus: high efficiency of expression， safety，simple construction and operation， high efficiency of transduction， can a wide range ofmammalian cells to infect， it will be more advantage than others as the carrier of the genetherapy. The genome of wild poxvirus has a lot of unnecessary genes such as TK gene， B18Rgene and VGF gene. The modified poxvirus with these genes knocked out， can’t replicate innormal cell. So the modified poxvirus is mucn better in targeting and killing cancer cells..TRAIL gene can specifically kill cancer cells through death receptors DR4and DR5.However， normal cells has a certain resistance to TRAIL activation. It means that TRAIL andits receptor has a higher activity in the cancer cells.Interleukin-24(IL-24) can selectively inhibitethe growth of tumor cells and induce its apoptosis， while it does no impact on normal cells. Asthe clinical data shows that IL-24has a significant anti-tumor effect， and the security of theIL24gene is very reliable. TRAIL-IETD-IL24double gene uses IETD to connect TRAIL geneand IL24gene. Ocolytic vaccinia virus which carrying TRAIL-IETD-IL24double gene infectedcells can activate caspase-8cell apoptosis pathway. IETD is a shear site of caspase-8apoptosispathway， and the double genes can express same amount of TRAIL and IL24. SoTRAIL-IETD-IL24combined the dual advantages of TRAIL and IL24can target and destructtumor cells better.On the basis of this study， we insert the TRAIL-IETD-IL24double genes to the pCBplasmid vector. We insert TRAIL-IETD-IL24gene into the oncolytic vaccinia virus TK gene distriction through homologous recombination method and build the purpose virus， OncoPox-TRAIL-IETD-IL24. Also we construct an oncolytic vaccinia virus carrying TRAIL gene(OncoPox-TRAIL)， an oncolytic vaccinia virus carrying the IL24gene (OncoPox-IL24) andoncolytic vaccinia virus carrying the EGFP gene (OncoPox-EGFP). Before picking plaquedetection， we test various virus protein expression. In a word， oncolytic vaccinia virusOncoPox-TRAIL-IETD-IL24will provide a new way for the clinical treatment of cancer.