Priming therapeutic anti-tumour immunity: the potential of cell-based vaccines and oncolytic viruses
Our research is centred on novel immune-based and viral biotherapies for cancer. Specifically, our preclinical and translational programme is focused on whether tumour cells can provide appropriate antigens for priming of anti-tumour immunity, and whether oncolytic viral therapy can trigger immunogenic tumour cell death. We have recently shown in both murine and human systems that immune priming is a critical component of reovirus and vesicular stomatitis virus therapy, and that unselected lymphocytes (as well as other cells) can deliver virus to lymph nodes to purge them of metastatic disease via both direct oncolysis and T cell priming against tumour associated antigens.
For clinical cell therapy, we have shown that dendritic cells can be delivered and tracked to lymph nodes in patients following intralymphatic delivery; this completed study will provide the platform for an evolving clinical programme using further cell-based strategies (+/- oncolytic viruses), guided by our laboratory data.
We are already trialling reovirus in patients, thus further providing the basis for taking combined immunotherapy/virus protocols into the clinic. Hence, by studying both model systems and human patient samples, we plan to develop the immune as well as cytotoxic potential of oncolytic viruses.
Figure 1. Tracking of dendritic cells following intralymphatic delivery
Figure 2. Death of melanoma cells following reovirus treatment
Qiao J, Kottke T, Willmon C, Galivo F, Wongthida P, Diaz RM, Thompson J, Barber G, Chester J, Selby P, Harrington K, Melcher A*, Vile R. Purging Metastases in Lymphoid Organs Using a Combination of Antigen-non Specific Adoptive T Cell Therapy, Oncolytic Virotherapy, and Immunotherapy. Nature Medicine. 2008; 14:37-44
West E, Morgan R, Scott K, Merrick A, Lubenko A, Pawson D, Selby P, Hatfield P, Prestwich R, Fraser S, Eves D, Anthoney DA, Twelves C, Beirne D, Patel P, O’Donnell D, Watt S, Waller M, Dietz A, Robinson P, Melcher AA. Clinical Grade OK432-Activated Dendritic Cells: In Vitro Characterisation And Tracking During Intralymphatic Delivery. Journal of Immunotherapy. 2009; 32:66-78
Prestwich RP, Errington F, Ilett EJ, Morgan R, Scott K, Kottke T, Thompson J, Morrison EE, Harrington KJ, Pandha HS, Selby PJ, Vile RG, Melcher AA. Tumor Infection By Oncolytic Reovirus Primes Adaptive Anti-Tumor Immunity. Clinical Cancer Research. 2008; 14:7358-66