Oncolytic immunotherapy is an emerging class of cancer therapeutics which exploit the ability of viruses to selectively replicate in and kill tumor tissue, while at the same time inducing a potent, patient-specific, anti-tumor immune response. Oncolytic viruses have the unique ability to generate a systemic immune response to the patient’s particular complement of tumor antigens, including neoantigens, with a truly off-the-shelf and practical approach. This potentially solves a current ‘holy grail’ of immune-oncology research, i.e. the development of truly practical patient-specific tumor neoantigen vaccines. Oncolytic viruses also potently activate innate immunity, including through TLRs and STING, meaning that altogether oncolytic immunotherapies bundle multiple immune oncology approaches into one. This particularly the case if, as for Replimune’s products, these are then used to also deliver multiple therapeutic proteins to tumors too.
While clear single agent clinical activity has been achieved with oncolytic immunotherapy, it is anticipated that particular synergy may be observed in combination with immune checkpoint blockade. Immune checkpoint blockade relies on a pre-existing inflamed tumor microenvironment and a pre-existing immune response to tumor neoantigens for clinical activity, which are only present in some patients. Oncolytic immunotherapy can induce both an inflamed tumor microenvironment and establish immune response to tumor neo-antigens and therefore combination of these two proven modalities is particularly logical and attractive.
Replimune is developing novel, proprietary oncolytic immunotherapies intended to improve both the direct anti-tumor effects of selective virus replication and the potency of the immune response to the tumor antigens released. Replimune intends to progress these rapidly through clinical trials and to combine these with checkpoint blockade at an early stage of clinical development.