Breakthroughs in the field of immuno-oncology have offered new hope for the possibility of safe, systemic, and durable tumor responses to an otherwise daunting disease. Promising immunotherapeutic approaches, such as adoptive cell therapy and immune checkpoint blockade, have gained a lot of attention recently as the new face of cancer therapy, but in practice, the reach of these strategies has proven to be extremely limited. Hepatocellular carcinoma (HCC), with a rising incidence and lack of effective therapies, represents a major worldwide health concern. Despite the inflammation associated with HCC, these tumors are characterized by a high degree of immune tolerance, due to a variety of interacting mechanisms, which present a hurdle for effective immunotherapeutic responses. In order for immune-based therapies to be effective for hepatic tumors, it is necessary to modulate the tolerogenic environment in the liver. Oncolytic viruses (OVs) can offer a novel approach to address the challenge of HCC by combining the benefits of direct tumor cell oncolysis with modulatory effects to break immune tolerance.
The central aim of ONCO-VAX is to address the current challenges in the field of immune-oncology through the rational design of a multi-mechanistic combinatorial approach based on the underlying biology of the tumor microenvironment. By first gaining a better understanding of the immune-suppressive microenvironment in HCC and the immune modulatory responses to OV therapy in HCC, we aimed to rationally design a therapeutic regimen using a novel chimeric vector, VSV-NDV, as the basis for a cutting edge and broad-acting oncolytic viral vaccine. In this project, the VSV-NDV technology is used as a viro-immunotherapeutic platform for HCC, with further engineering to express an immune checkpoint-modulating gene to ameliorate the immune-suppression, while simultaneously activating the antitumor immune response via induction of immunogenic cell death through virus-mediated oncolysis. As an additional layer of therapy, a novel anti-cancer vaccine is under development, in which antigen presenting cells, called dendritic cells (DCs), are prepared in a unique manner, whereby they will be activated and loaded with antigens using VSV-NDV-infected tumor oncolysates ex vivo.
This multifaceted approach represents an innovative and crucial step forward revolutionizing immune oncology and providing new hope to cancer patients with immune-suppressive solid tumors.
