The proposed therapeutic vaccine for Non-Hodgkin's Lymphoma (NHL) is part of XEME Biopharma's goal of designing liposome-based vaccines that can deliver at the same time both the tumor-specific antigen (Ag) and potent immunostimulators. The novel liposome described in the grant proposal is self-assembled during an overnight incubation from unilamellar nano-vesicles made of a single synthetic lipid, cytokine(s) capable of causing coalescence of the vesicles and tumor-specific Ag. The resulting multilamellar coalescence vesicle (MLCV) liposomes form a milky suspension of billions of lipid vesicles per milliliter that upon inoculation subcutaneously will distribute and release both the antigen and immunostimulator to the relevant immune cells. The proposed research in this Phase I SBIR grant application is focused on use in XEME's vaccine of the cytokine GM-CSF, a potent stimulator of antigen presenting cells. The first studies will examine the ability of GM-CSF to aggregate and induce coalescence of DMPC nano-vesicles, alone and then in the presence of Ag. The resulting MLCV vaccine will be tested for its ability to protect mice against a lethal challenge of murine lymphoma cells. Following this, a second cytokine which stimulates T lymphocyte immune responses will be added to GM-CSF and Ag to form an MLCV vaccine with dual immunostimulant activity. This vaccine will be tested in comparison to single cytokine vaccines in a murine lymphoma model to assess the value of cytokine co-entrapment for vaccine efficacy. The results obtained from this SBIR Phase I project will provide the foundation for further research into active immunotherapy of NHL and other cancer indications using liposomes charged with tumor antigens and cytokine immunostimulators. Therapeutic cancer vaccines are a promising "fourth dimension' to cancer treatment regimens already consisting of surgery, radiation and chemotherapy/mAb therapy. Unlike the current treatments, such vaccines promise to be much less toxic and invasive. A therapeutic vaccine for Non-Hodgkin's Lymphoma will provide a new treatment modality for the 55,000 new cases of the disease diagnosed in the US each year as well as the over 300,000 persons who are currently under long-term treatment or in temporary remission.
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