The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: December 23, 2011

Super-Selective Oncolytic Virus

Ottawa Hospital Research Institute ♦ Published in Molecular Therapy (npg), December 20, 2011

More on oncolytic viruses this week but not with VSV this time, but rather the poxvirus JX-594. This particular virus, while having an excellent therapeutic index against multiple solid tumour types, is not that well understood. Researchers seeking to understand the mechanisms underlying its exquisite cancer cell selectivity identified multiple interactions. Three model systems were investigated, including primary normal and cancer cells, surgical explants, and mouse tumour models. It was found that selectivity of JX-594 was driven by multiple factors; the first time selectivity has been attributed to more than one specific mechanism. Among these factors were virus replication activation by the EGFR/Ras signaling pathway, cellular thymidine kinase levels (the virus is engineered to be responsive to TK so this was expected), and similar to VSV, hyporesponsiveness to type-I interferon. These finding will allow for the generation of more selective and potent oncolytic viruses.

Immunomodulators Enhance Polyfunctionality of T Cells Following Vaccination

McMaster Immunology Research Centre ♦ Published in Molecular Therapy (npg), December 20, 2011

Recombinant human adenovirus vaccines are capable of producing memory CD8+ T cell populations, however these populations lack polyfunctionality; in response to antigen stimulation they are not able to produce multiple different cytokines and chemokines. Researchers at McMaster have discovered that inhibiting mammalian target of rapamycin (mTOR) while stimulating OX40 alters not only the magnitude of T cell response, but also its phenotype and functionality. mTOR inhibition modulates differentiation of T cell pools while stimulation of OX40 enhances the process of costimulation. The addition of immunomodulators elicited greater immunity against multiple virus challenges in a mouse model, but was contingent upon sufficiently long transgene expression from the adenovirus under study.

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