Chimeric CD80-SA as a Novel Cancer Vaccine

DESCRIPTION (provided by applicant): Cancer is one of the major causes of death in the U.S. and many developed countries with an estimated economic burden of over 100 billion dollars in direct and indirect costs in the U.S. alone. Although surgery, chemotherapy, and radiotherapy are commonly used treatment modalities, these therapies not only fail to effectively manage cancer, but also are associated with adverse side effects due to their lack of specificity against cancer cells. Therefore, there is an acute need for the development of more effective and tumor-specific therapies for the treatment and prevention of cancer. Immunotherapy has recently gained impetus as a cancer treatment modality due to its specificity, safety, and its ability to generate immunological memory that can safeguard against recurrences. Tumor cells genetically modified to express costimulatory molecules, such as CD80, have been shown to be effective in preventing tumor development and eradicating existing tumors when used as a vaccine in preclinical studies. This approach has been the subject of several recent Phase l/ll clinical trials with encouraging results. However, the expression of costimulatory molecules via gene therapy is elaborate, inefficient, expensive, and associated with several safety concerns. To circumvent these problems, Apolmmune, Inc., is developing vaccines based on a novel proprietary technology, designated as ProtEx(tm), that allows for the display of exogenous proteins on the surface of tumor cells in a rapid (<2 hrs) and efficient (100% of the targeted cells) manner without the costs or safety issues inherent to gene therapy. ProtEx involves the generation of chimeric proteins with core streptavidin, biotinylation of the cell surface, and decoration with chimeric proteins. Most importantly, since the chimeric proteins exist as oligomers they can effectively crosslink their counter receptors on relevant immune cells for the delivery of potent signals, thereby generating effective anti-cancer immune responses. Proof-of-principle for a proprietary vaccine (ApoVax(tm)) based on the use of tumor cells decorated" with a chimeric human CD80 molecule (CD80-SA) has been generated in a preclinical tumor model and ex vivo clinical studies. This application is intended to support the development of ApoVax(tm)as a lead vaccine product that will eventually be used in Phase I clinical trials, which will be the subject of a Phase II SBIR application. It specifically focuses on i) high yield production, purification, and characterization of the CD80-SA protein, ii) developing a final stable formulation for the protein and ApoVax(tm) vaccine, iii) determining the most effective treatment regimens in preclinical studies, vi) performing toxicological studies, and v) producing pilot cancer vaccine materials under current GMP conditons. The long term success of this project may allow for the development of ApoVax(tm) as a multi-million dollar cancer vaccine product and improvement in the longevity and quality of life for millions of cancer patients.