Abstract
A recombinant vaccinia virus VVdGF-ApoS24/2 expressing apoptin selectively kills human cancer cells in vitro [Kochneva et al., 2013]. We compared the oncolytic activity of this recombinant with that of the parental strain L-IVP using a model of human A431 carcinoma xenografts in nude mice. Single intratumoral injections (2×10^7 PFU/mouse) of the viruses produced a dramatic decrease in tumor volumes, which was higher after injection of apoptin-producing virus. The tumor dried out after the injection of recombinant while injection of L-IVP strain resulted in formation of cavities filled with cell debris and liquid. Both viruses rapidly spread in xenografts and replicate exclusively in tumor cells causing their destruction within 8 days. Both viruses induced insignificant level of apoptosis in tumors. Unlike the previously described nuclear localization of apoptin in cancer cells the apoptin produced by recombinant virus was localized to the cytoplasm. The apoptin did not induce a typical apoptosis, but it rather influenced pathway of cell death and thereby caused tumor shrinkage. The replacement of destroyed cells by filamentous material is the main feature of tumor regression caused by the VVdGF-ApoS24/2 virus. The study points the presence of complicated mechanisms of apoptin effects at the background of vaccinia virus replication.
Highlights
Oncolytic viruses are characterized by the ability to recognize and selectively kill cancer cells
The present study aims the assessment of oncolytic properties of the apoptin-producing recombinant Vaccinia virus (VACV) (VVdGF-ApoS24/2) in the model of nude mice xenografts of the human A431 epithelioid carcinoma cells, in comparison with the parental L-IVP virus strain
Virus replication in A431 cells in vitro and in vivo. Both the L-IVP and the apoptin-expressing recombinant VACV strain VVdGF-ApoS24/2 have demonstrated the ability to replicate in the A431 carcinoma cells in vitro, the yield of the recombinant virus was lower (Fig. 1A)
Summary
Oncolytic viruses are characterized by the ability to recognize and selectively kill cancer cells. The ability to replicate preferentially in malignant cells is a property of many viruses belonging to a variety of viral families. The recombinant “armed” oncolytic viruses are being designed to carry additional therapeutic proteins that enhance the efficiency of specific destruction of the malignant cells. Such viruses destroy tumor cells during the replication, and serve as delivery vehicles providing the release of therapeutic molecules inside the tumor. The effector molecules introduced into the viral genome aim either at the direct killing of cancer cells [11], or at an enhancement of antitumor immune responses [12]
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