Breaking the immunosuppressive shield of solid tumors of gastrointestinal origin: Multi-armed oncolytic vaccinia virus for in situ vaccination
Hematology, Oncology
Final Report Abstract
A strong lymphocyte infiltration has been reported to be associated with an antitumor response and improved clinical outcome. But the majority of patients with gastrointestinal malignancies present pure immune cell infiltrated tumors with a highly immunosuppressive microenvironment. The application of oncolytic vaccinia virus with induction of immunogenic cell death offers an effective strategy to overcome less immunogenic tumors. Viral mediated cell death results in the release of potent danger signals and cross presentation of tumorassociated antigens, resulting in antitumor innate and adaptive immunity. Over the past decade the Bartlett group engineered new vaccinia virus constructs chemokine or cytokine armed with the goal to enhance the anti-tumor immune response. To determine the most T cell attracting virus construct, the T cell immune response has been studied in a murine colon tumor model. Based on the sudies about virus induced tumor specific T cells a novel approach has been developed using vaccinia virus induced tumor infiltrating T cells for ex vivo expansion and adoptive T cell transfer in a pre-clincial model. Intratumoral application of cytokine-armed oncolytic vaccinia virus promoted T cell infiltration into the tumor microenvionment. The virus induced T cells were highly tumor specific and kept their therapeutic potential when expanded ex vivo and transferred into tumor bearing mouse. The report presents a new strategy to promote intratumoral T cell infiltration and to generate tumor specific T cells in the tumor microenvionment for adoptive T cell transfer.
Publications
- (2017) 'Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives', Front Immunol, 8, pp. 555
Guo, Z. S., Liu, Z., Kowalsky, S., Feist, M., Kalinski, P., Lu, B., Storkus, W. J. and Bartlett, D. L.
(See online at https://doi.org/10.3389/fimmu.2017.00555)
