Oncolytic viral therapies act to re-invigorate the host’s own immune system from which the cancer has escaped control by a process known as immunoediting. Adaptive immune cells such as CD8+ and CD4+ T cells are unable to exert their effects, both as a result of direct suppression and of exclusion. A number of therapies have been trialled, and some licensed, seeking to address the immunological deficiencies in cancer, but these have a number of drawbacks. Immune Checkpoint Inhibitors (ICIs), despite having achieved some exciting results in some types of cancer, only elicit responses in around 25% of patients. In addition to induction of powerful anti-tumour immune responses and tumour cell lysis, oncolytic viruses have the potential to synergise with ICIs, increasing the therapeutic effect of these molecules. However, oncolytic viruses in trial have a number of potential drawbacks, from limited tropism with some vectors, to a widespread inability to deliver strong CD8+ and CD4+ T cell responses within the tumour following systemic delivery.
This technology incorporates a rationally developed oncolytic Vaccinia virus, specifically engineered to improve safety, tumour tropism and induce potent anti-tumour immune responses. An additional feature of the viral platform is the enhanced ability to produce Extracellular Enveloped Virus (EEV), improving the ability of the virus to spread and propagate within the host. The viral platform includes a stable expression cassette from which exogenous payloads can be expressed. Incorporation of pro-immune molecules within this cassette has been demonstrated pre-clinically to significantly improve anti-tumour innate and adaptive immune responses. Specifically, this platform enhances intratumoural accumulation of CD8+ and CD4+ T cells, improves development of systemic effector CD8+ responses, enhances natural killer (NK) cell populations and is able to reprogram immunosuppressive M2 phenotype macrophages common in the TME to an immunostimulatory M1 phenotype. Coupled with an improved delivery protocol, this technology platform offers a unique, potent and systemically deliverable oncolytic viral therapy that can additionally broaden the effectiveness of clinically available ICI therapies.
Oncolytic viral therapies act to re-invigorate the host immune system from which the cancer has escaped by immunoediting. The action of viral oncotherapy has a number of aspects:
i) Direct viral lysis of cancer cells;
ii) Induction of immunogenic cell death pathways and danger signals that provoke immune activation;
iii) Release of large numbers of tumour-associated and tumour-specific antigens;
iv) Generation of a revitalised and robust tumour-specific immunity against cancer cells.
Systemic (IV) delivery and action, allowing treatment of metastases as well as primary tumour.
Clearly demonstrated enhanced CD8+ effector T cell responses in animal models
Breaks down immunoexclusive and immunosuppressive tumour microenvironments (TME)
Demonstrated potentiator of PD-1 inhibitor in immunologically inert pancreatic cancer
Unaffected by hypoxia. Fully optimised and widely validated, demonstrated safe backbone virus with ability to express exogenous proteins
Wide tropism, applicable to a range of cancers