Dendritic cells transfected with RNA as cancer vaccines: Research Question: Can we develop a novel vaccine strategy that is translatable and broadly applicable to all cancer patients, including patients with low tumor burden? Summary: We tested the hypotheses that: 1] Immunization with a broad repertoire of tumor antigens isolated form cancer cells is superior to using defined tumor antigens. 2] Loading antigen on DCs in the form of tumor mRNA is highly effective and provides unique advantages over other forms of tumor antigen, specifically, the ability to amplify the antigenic content of a small number of tumor cells. In a pioneering study, our group demonstrated that dendritic cells loaded with unfractionated total RNA isolated from tumor cells stimulates tumor immunity both in murine tumor models and in in vitro human assays (patent awarded in 1998). A company, Argos Therapeutics was established in Durham, NC to commercialize this approach.
Modulation of immune responses to enhance tumor-specific immunity: Research Question: How can the therapeutic benefit for patients treated with RNA-transfected dendritic cells be improved? Summary: Modulating immune responses by blocking inhibitory immune receptors and activating stimulatory immune receptors on T cells enhances tumor-specific immunity. Systemic administration of antibodies (Abs) targeting inhibitory immune receptors enhanced the stimulation of immune responses in mice. However, clinical use of such Abs is limited by toxicity. We have developed an approach for local modulation of immune responses by delivering RNA encoding immune modulating proteins (Abs or receptor-binding ligands) regionally at the site of T cell activation.
Novel vaccine strategies: Research Question: How do we develop an effective vaccine strategy that is NOT time-, labor- and resource-intensive? Summary: A drawback of dendritic cell-based vaccination is that the process of harvesting, culturing and loading dendritic cells with antigens is time-, labor- and resource-intensive. We have demonstrated an innovative method of vaccination as a proof-of-concept in a study by loading mRNA encoding a tumor antigen onto whole blood cells. This approach circumvents the time-consuming cell culture and leukapheresis required for dendritic cell vaccines and can be completed in 1 to 2 hours instead of 7 to 9 days.
Oncolytic poliovirus immunotherapy: Research Question: Does regional cytoxicity with oncolytic poliovirus stimulate innate immune events that promote an in situ vaccine effect? Summary: Matthias Gromeier has pioneered an oncolytic poliovirus (OncPV) therapy, PVSRIPO