A Phase II SBIR program of preclinical development is proposed for the development of an active specific immunotherapeutic called Cellarium" for treatment of glial cell-based cancers. Successful completion of this project will confirm therapeutic effect and pre-clinical safety of the vaccine in preparation for first-in-human studies Upon demonstration of safety and efficacy, the Cellarium vaccine will provide a greatly-improved, targeted treatment for glioma patients, for whom current treatments can be debilitating, painful and expensive. Gliomas are widespread deadly diseases for which current therapies are inadequate. In the US gliomas accounted for 44% of the 22,070 cases of brain and other nervous system cancers diagnosed and 12,920 associated deaths in 2009. Recent studies have shown increasing incidence of glioma in US adults. Gliomas are predominantly treated today with an aggressive three-step protocol of surgery, chemotherapy and radiation. Despite this regimen, patients with Glioblastoma Multiforme (GBM), the most common and deadly malignant brain tumor, still have a median survival of less than 15 months. Moreover, the estimated cost of treatment for each patient with a malignant brain tumor ranges from $30,000 to several hundred thousand dollars annually. Originally, this technology approach was conceived in the laboratory of Dr. David Mooney at the University of Michigan (who is now at Harvard University). The Cellarium technology is the result of work at InCytu in both the melanoma and glioma models that has led to new insights which transcend the original discoveries at Michigan and Harvard and have led to a more effective and reliable product. The Cellarium is an in situ therapeutic vaccine which incorporates biological cofactors and patient-specific cell lysate, attracts dendritic cells (DCs), exposes them to the tumor specific antigens, and then releases them to direct a strong, targeted immune response against malignant tissue. Phase II aims are: (1) to manufacture Cellarium using equipment and methods purpose designed to yield CNS specific product sized for both the murine and human sized brain and confirm Phase I results of the Cellarium for Glioma in both murine and porcine preclinical models;(2) to develop formal Standard operating Procedures needed for submission to the FDA and validate manufacture and QC of the devices then perform a pre-GLP study needed for discussions with the FDA;(3) to conduct GLP safety and efficacy study in preparation for the filing of an IND. If Phase II studies are successful, the Cellarium" vaccine will continue to be developed through clinical trials with the eventual goal of scaling manufacture in the US and selling as a commercially available specific immunotherapeutic vaccine to treat glioma patients.
Glioma is a growing public health problem (12,920 deaths in 2009);current therapies are expensive (>$30k with severe side effects) and difficult (median survival <15 months, very few remissions) to treat. A breakthrough immunotherapy called Cellarium showed very promising results (955% increase in median survival) in a rat model performed under a Phase I SBIR program. This project will complete pre-clinical development of the Cellarium glioma therapeutic vaccine in preparation for filing an IND and a first-in-man study.