Several modifications have been made to OncoViron to enhance its specificity and efficacy, including the fusion of the oxygen-dependent degradation (ODD) domain of HIF-1α with the E1a protein to restrict its replication only in the hypoxic TME, silencing the E1B55K protein to ensure its selective replication in TP53-inactivated tumors, the triple chimerization of three serotype adenoviruses with enhanced infectivity and viability, and the incorporated expression of IL-12, IFN-γ, and CCL5 in OncoViron to enhance the anti-tumor immune response. Here, TP53 is linked to neoplasm.