To ensure Moffitt continues to be a leader in ground-breaking research on infection-related cancers and therapeutic vaccines, CIIRC has developed a grant program for funding innovative pilot projects. These grants provide support for high risk, high reward projects designed to generate pilot data that can lead to large NIH funded awards in the area of immunizations, infection and cancer.
Findings have been presented at conferences and published in peer-reviewed journals. More importantly, these pilots are moving the field of infection and cancer research forward, with results that could possibly lead to the next dramatic improvements to the diagnosis and treatment of cancer. The most recent pilot projects are described below:
Role of gut microbiome in response to dendritic cells and HER2 targeted therapies
Breast cancer is the second leading cause of death among women in the United States. Among women diagnosed with breast cancer, 15-20% will be positive for the gene called human epidermal growth factor receptor-2 (HER-2), which is responsible for the growth and proliferation of the tumor.
We are currently conducting a clinical trial evaluating the outcome of treating women with HER-2pos breast cancer with antibodies targeting HER-2 prior to surgery. We have also developed a way to train the body’s own immune system to recognize and mount an immune response against HER-2pos tumors, by removing particular types of immune cells, called dendritic cells, "training" them to recognize the HER-2 protein, then reintroducing them to the patient.
Importantly, the number and type of beneficial bacteria in the gut (the "microbiome") are important regulators of a robust immune response to any invading pathogen, including tumor cells. By evaluating the makeup of this microbiome among patients that respond well and patients that respond poorly to treatment, we can gain insight into ways to increase a positive response via changing the makeup of the microbiome.
This provides a new, non-invasive method of increasing response to immunotherapy over conventional chemotherapy, radiation, or surgical procedures.
Optimizing vaccine-based immunotherapy using virtual treatment optimization solver (VirTuOso)
The goal of cancer vaccines is to increase response of patients’ immune system. When the vaccines are injected locally into the tumor (intralesional injection), they can induce tumor-specific immune response by increasing tumor infiltration by the T cells. Our preliminary studies showed that intralesional injection of bacteria-derived pAc/emm55 vaccine significantly delayed growth of B16 melanoma compared to the control group and improved the overall survival.
However, further studies are necessary for designing the optimal treatment protocols to maximally enhance anti-tumor T cell responses. In this proposal we will use computer simulations integrated with cell culture and mice experiments to determine optimal schedules and dosages of therapy combining the pAc/emm55 vaccine and PD-1 blockade in melanomas.
These studies will increase our understanding of the immune cell response to cancer vaccines, will establish a verified protocol for optimizing vaccine-based immunotherapies in solid tumors, and, in particular, will provide a proof of principle in treatment optimization using the pAc/emm55 vaccine and PD-1 blockade in melanomas. While the proposed studies are pre-clinical, the developed treatment combinations have a high translational potential, and, in the future, we will work to extend our optimization tools to clinical application.