Abstract

The development of vaccines for melanoma has been accelerated by the identification of melanoma-associated antigens, a better understanding of basic immunologic principles, and the ability to construct complex vectors for immunization. The location and context in which T-cell priming occurs significantly influences the type and magnitude of immune response. Furthermore, there is a delicate balance between the generation of tumor-specific immunity and the emergence of tumor escape variants. We have focused on the direct intra-tumoral delivery of poxvirus vaccines expressing costimulatory molecules as a strategy for overcoming local immunosuppression in the treatment of established melanoma. Poxviruses provide potent danger signals and, in the presence of costimulation, local administration provides a mechanism to prime tumor-specific T-cell responses. The clinical application of this approach will likely depend on the ability to induce systemic anti-tumor immunity following local injection and we are evaluating this in current clinical trials. These studies may have important implications for the design of vaccine strategies for melanoma and other tumors.