Fusion proteins for promoting an immune response, nucleic acids encoding same, and methods of making and use thereof

Abstract

Disclosed herein are compositions, cells, kits, and methods for inducing an immune response in a subject. The compositions can be used as vaccines or vaccine adjuvants against cancer (e.g., melanoma, glioma, prostate, breast) and infectious diseases (e.g., therapeutic and preventative vaccination for viruses), and can be used in cell-based therapies for preventing and treating disorders such as cancer and infection. The compositions, cells, kits and methods involve one or more nucleic acids that encode one or more LMP1 fusion proteins (chimeric proteins), and in a typical embodiment, synergistic activation of immune responses by a combination of two or more LMP1 fusion proteins. By combining multiple fusion proteins composed of the LMP1 protein aggregation (transmembrane) domain and the cytoplasmic domain of toll-like receptors (TLR), proteins, Tumor Necrosis Factor Super Family Receptors (TNFSFR) proteins, PRR proteins, or adapter proteins that are involved in innate/adaptive immune signaling pathways, introduction of the fusion proteins into dendritic cells or other antigen presenting cells results in synergistic activation.