Intratumoral Approaches for the Treatment of Melanoma

There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors. In addition, there are several novel methods for local drug delivery, including direct injection, image-guided, electroporation, and nanodelivery techniques under study. The approval of talimogene laherparepvec (Imlygic), an attenuated, recombinant oncolytic herpesvirus, for melanoma treatment is the first intratumoral agent to receive regulatory approval for the treatment of patients with melanoma. This review will focus on the rationale for intratumoral treatment in melanoma, describe the clinical and safety data for some of the agents in clinical development, and provide a perspective for future clinical investigation with intratumoral approaches. Melanoma has been a paradigm tumor for progress in targeted therapy and immunotherapy and will likely also be the tumor to establish the therapeutic role of intratumoral treatment for cancer.