Research On Oncolytic Adenovirus Carrying IL-24in Lymphoma Cell

Oncolytic adenovirus can specifically target tumor cells, has the ability ofreplication and proliferation in the host, and induces the lysis of tumor cellsultimately. And then the progeny virus spreads to the surrounding cells, leading tothe lysis of tumor cells persistently and eventually the infection of the whole tumortissue, which results in the elimination of the tumor. As one of the efficientvectors, oncolytic adenovirus also can carry exogenous tumor-suppressor gene andinfect tumor cells efficiently. The tumor suppressor proteins are amplified with thevirus amplification with thousands of times and play a dual effect of gene therapyand viral therapy.IL-24/Mda-7, a kind of secreted protein with general anti-tumor properties,may have potential “bystander effect”, increase radiation lethality, induceimmune-regulatory response, inhibit tumor angiogenesis and drive tumor cell toapoptosis. The tropism of adenovirus infection is determined by the fiber proteinencoded by adenovirus. Adenovirus type5(Ad5) is a common vector in genetherapy, with the infection of combination of Fibre and the cell surface coxsackieand adenovirus Virus receptor (CAR). Cells with low expression of CAR aredifficult to be infected. Tumor cells in blood are usually low-CAR expressing,which limits the application of Ad5.Human adenovirus serotype11(Ad11), with a different fiber from Ad5’s, canentry cells through a path of a secreting complement regulatory proteins CD46(aspecific membrane protein) in cytomembrane. Ad11adenoviral vector is animportant tool for cancer therapy, especially lymphoma.The purpose of this experiment was to assesse the anti-lymphoma effect whilekilling lymphoma cell and overexpressing IL-24with the oncolytic adenovirusnamed AdCN205-11-IL-24.In this chimeric oncolytic adenovirus Ad5/F11vector, adenovirus E1A gene,lacking of24bp in the genome, is controlled by the human telomerase reversetranscriptase (hTERT) promoter.As a result, the chimeric adenovirus of Ad5skeleton and Ad11fiber is as safe as Ad5, while targeting the same aimed cells as Ad11. In vitro experiments showed that:compared with the control,AdCN205-11-IL-24can more strongly target CD46+tumor cells, replicate in thetarget cells, overexpress IL-24and kill garget cells. This research showed thatAdCN205-11-IL-24is a tumor specific replicating virus which can combines virustherapy and gene therapy together.It shows strong anti-tumor effects especiallyanti-lymphoma.The experiments data indicate it could exert potential anti-tumoractivity and offer a novel approach for treatment of cancer.