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A genetically-engineered, replication competent, oncolytic serotype 5/3 capsid-modified adenovirus and encoding for the T-cell immunostimulatory cytokines tumor nerosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2), with potential oncolytic and immunostimulating activities. Upon administration of TNFalpha/IL-2-encoding oncolytic adenovirus TILT-123, the oncolytic adenovirus binds to specific Ad3 receptors that are highly expressed on certain tumor cells and selectively infect and replicate in tumor cells, and express TNF-alpha and IL-2. The oncolytic virus itself induces a viral-mediated tumor cell lysis which may result in the activation of a systemic immune response against tumor-associated antigens. The expressed proteins may further stimulate the immune system to modify the immunosuppressive tumor microenvironment (TME) and induce a cytotoxic T-lymphocyte (CTL) response against the tumor cells. TILT-123 is designed to replicate only in cells with defects in the p16/Rb/E2F pathway, attributed to a mutation common in many solid tumors. Replacement of the Ad5 capsid protein knob with a knob domain from serotype 3 causes higher transduction in cancer cells as compared to normal cells.
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