The Viruses, Immune stimulation and RNA Interference in Oncology Network (VIRION) is focused on the development of a novel therapeutic regime by combining immune therapy with oncolytic virotherapy and RNA interference techniques.
Recent clinical successes have shown the immune system to be a powerful ally in the fight against cancer. While surgery, chemotherapy and radiation therapy remain the first lines of treatment for most tumors, immunotherapy regimens are achieving astonishing clinical successes. Furthermore, recent studies showed that pre-existing lymphocytic infiltration of tumors is associated with superior prognostic outcomes in a variety of cancers and might improve cancer therapies targeting immune checkpoints. A new development in the immunotherapy field is adoptive cell therapy (ACT). In ACT, lymphocytes from cancer patients are expanded ex vivo into more favorable numbers; often modified genetically or stimulated to relieve immune suppression; and infused back into the patient. In clinical trials, ACT has resulted in anti-tumor responses.
However, immune suppression in the tumor microenvironment limits the efficacy of immunotherapy and remains a major hurdle. Therefore, we aim to potentiate the antitumor immune reaction in the tumor microenvironment, through the combination of immune therapy and oncolytic virotherapy. Oncolytic viruses are developed to specifically target and destroy tumor cells. In pre-clinical models, oncolytic adenoviruses have proven a powerful tool in the elimination of tumors, not only by their direct lytic effects but also by their triggering of a subsequent tumor inflammation and enhanced lymphocytic infiltration. VIRION addresses how these immune responses can be further enhanced by addition of immune modulating factors and/or siRNA targeting cancer genes that play a role in immune suppression.
Our studies have demonstrated that oncolytic adenovirus are able to modulate the tumor micro-environment by themselves resulting in increased immune activity. This can be further enhanced by checkpoint blockers (anti-PD1 or anti-PDL1) and adoptive cell therapy. Although these latter elements by themselves have impact on the tumor microenvironment and stimulate anti-tumor responses, combining these with oncolytic adenovirus results in a further enhancing of the anti-tumor immune response. In addition different siRNA targets and modulating genes have been identified which will can give rise to a new generation of oncolytic adenoviruses with enhanced potency and abilities to induce anti-tumor immune responses.
