Alphavirus replicon particles expressing melanocyte differentiation antigens are effective vaccines for melanoma (41.55)

Abstract

Abstract Melanocyte differentiation antigens are attractive candidates for melanoma immunotherapy, but because they are expressed by malignant cells as well as their normal counterpart eliciting effective immune responses is challenging. Here we evaluated an alphavirus replicon vector system as a potential melanoma immunotherapy. Use of propagation-defective virus-like replicon particles (VRP) based on an attenuated strain of Venezuelan equine encephalitis (VEE) virus is especially attractive because VRP express heterologous proteins to high levels and target expression to dendritic cells. VRP vaccines have been shown to elicit both humoral and cellular immune responses to the vectored gene products in many animal disease models and in phase I clinical trials. The efficacy of VRP expressing the melanocyte differentiation antigens tyrosinase, gp100 or TRP-2/DCT was analyzed against challenge with the poorly immunogenic and highly aggressive B16 murine melanoma. TRP-2/DCT-expressing VRP were the most effective in delaying tumor occurrence when compared to the other antigens tested. Although both TRP2/DCT-specific CD8+ T cells and IgG are induced, the data suggest that B-cells may play a more important role in the effector phase of tumor protection. These studies demonstrate that VRP vaccines present a promising approach for melanoma immunotherapy.