About Cancer Immunotherapy. Cancer is the second most common cause of death in the US, exceeded only by heart disease. Its global burden is expected to rise to 22 million new cases by 2030. Currently, there is only one FDA approved cancer vaccine, PROVENGE® (sipuleucel-T) a personalized therapy for prostate cancer patients. However, the field of immune-oncology has received new momentum with the discovery and initial launch of monoclonal antibodies (Mabs) called immune checkpoint inhibitors (ICIs). Tumors hijack the body’s natural immune checkpoints by overexpressing immune checkpoint ligands (proteins that bind to and activate the inhibitory activity of immune checkpoints), as a mechanism of immune resistance, especially against the T cells that are specific for tumor antigens and can kill cancer cells. ICIs block the interaction of Immune checkpoints with their ligands on tumor cells, allowing poorly functional T cells to resume proliferation, cytokine production and killing of tumor cells.
Unlike conventional therapies (e.g. radiation, chemotherapy, antibody, etc.), cancer vaccines have the potential to induce responses that not only result in the control and even clearance of tumors but also establish immunological memory that can suppress and prevent tumor recurrence. Convenience, safety, and low toxicity of cancer vaccines make them invaluable tools to be included in future immunotherapy approaches for treating tumors. Currently, there are only a few vectored cancer vaccines being tested in combination with ICIs, all of which are in early clinical stages.
Our Immuno-Oncology Development Efforts. GeoVax has established a collaboration with Dr. Olivera Finn, a leading expert in cancer immunotherapy at the University of Pittsburgh. She was the first to show that many tumors express an abnormal form of cell surface-associated Mucin 1 (MUC1) protein could be recognized by the immune system as foreign. Given this, we are using our MVA-VLP vaccine platform to deliver abnormal forms of MUC1 (e.g. hypo-glycosylated forms found in tumors) (Figure 1) with the goal of raising protective anti-tumor antibodies and T cell responses in cancer patients.
Figure 1. MVA-MUC1-VLP Vaccine. Hyper- and hypo-glycosylated forms of MUC1 is expressed on the surface of the VLPs in MVA-VLP-MUC1 infected cells.
We are also collaborating with ViaMune, Inc. who has developed a fully synthetic MUC1 vaccine candidate (MTI) (Press Release). The collaboration will assess each companies' vaccine platform, separately, and in combination, with the goal of developing a tumor MUC1 vaccine that can produce a broad spectrum of anti-tumor antibody and T cell responses. The resulting MUC1 vaccine will be combined with checkpoint inhibitors (CPIs) as a novel vaccination strategy for cancer patients with advanced MUC1+ tumors.
We have already produced an MVA-VLP-MUC1 vaccine candidate, demonstrated VLP production by electron microscopy using MUC1 immunogold staining and showed that the VLPs express hypo-glycosylated MUC1 in human 293T cell lines. On August 30, 2017, we presented our preliminary results from studies of GeoVax’s MUC1 cancer vaccine in collaboration with ViaMune, Inc. at the Advances in Vaccine Technologies session at the Immuno-Oncology Summit in Boston, MA. GeoVax and ViaMune are each developing product that target an abnormal form of the autologous cell surface-associated protein, Mucin 1 (MUC1), which is overexpressed in metastatic cancers (e.g. breast, pancreatic, lung, and ovarian cancers) and circulating tumor cells and which is used as a diagnostic marker for cancer progression. Due to overexpression and/or aberrant glycosylation of MUC1, this “tumor-associated antigen” (TAA) is often recognized as abnormal by a patient’s immune system but is not sufficiently immunogenic to trigger an effective immune response shown to be associated with significant increase in overall survival of patients. Therefore, this or any TAA must be presented to the body in a different form, or in a different way, to recruit the patient’s own immune system to fight the cancer. GeoVax and ViaMune are collaborating with the goal of developing a tumor MUC1 vaccine that can produce a broad spectrum of anti-tumor antibody and T cell responses. In a human MUC1 colon adenocarcinoma mouse tumor model, groups of hMUC1 transgenic mice with established tumors were treated with MTI (ViaMune’s synthetic vaccine), MVA-VLP-MUC1 (GeoVax’s viral-vectored vaccine) or a combination of both. All treatment groups received an immune checkpoint inhibitor in the form of an anti-PD-1 antibody. The preliminary results from two studies indicate that a combined vaccine approach can increase the activity of anti-PD-1 therapy. The studies were performed by the laboratory of Dr. Pinku Mukherjee, PhD, at the University of North Carolina at Charlotte. These data demonstrated a potentially synergistic effect between the GeoVax and ViaMune vaccines. This study gives us the scientific justification to pursue additional investigation of our approach, and we intend to seek funding to vigorously pursue development of the combined MVA-MTI technologies for the treatment of multiple cancer indications.”
It is anticipated that within 2 years we will be able to file an IND with the FDA and initiate a Phase 1 trial in a limited number of cancer patients.