The broad research goals for the applicant's pre-doctoral education are to learn how the immune system works in a cancer disease state and how to use this knowledge to develop novel cancer immunotherapy. The long term objective is to improve on cancer immunotherapeutic approaches using isolated cell-specific peptides.
The specific aims are 1) to develop dendritic cell (DC) based cancer vaccines and 2) to test the best format in a mouse tumor model. #1) The Brown lab has developed a peptide presenting-phage library panning protocol by which cell-specific peptides can be isolated without prior knowledge of the cell surface. By utilizing this protocol on XS52 immature DC line, peptides were isolated that can directly target immature DCs. This group of immune cells is important for initiating an immune response against a novel antigen.
The aim i s to use the isolated XS52 targeting peptides to create and test three cancer antigen delivery mechanisms to DCs in order to induce an anti-tumor immune response. The methods are: 1) A genetic vaccine, 2) a peptide-antigen conjugate, and 3) an antigen loaded liposome. All methods are clinically relevant and will test whether the DC targeting peptides can improve on current cancer vaccines. #2) The vaccination formats mentioned in the previous aim will be tested for induction of a humoral and cell mediated immune response. The best performing format will be used in a mouse tumor model to test the prophylactic and therapeutic potential of the cancer vaccination. A group of mice will undergo vaccination prior to injection of 4T1 mouse breast cancer cells while another group will undergo tumor formation prior to initiation of vaccination. This will test whether the vaccine is better suited to prevent tumors, to treat already existing cancers, or for both. The development of novel cancer therapeutic approaches is in agreement with the goals stated by the National Cancer Institute for the advancement and development of novel cancer therapies. Cancer is currently the 2nd leading cause of death in the United States, making it an important public health issue. Development of novel cancer treatments through generation of dendritic cell-based vaccines will advance cancer immunotherapy while reducing the negative side effects caused by current treatments.
