Cell-based vaccination against melanoma--background, preliminary results, and perspective

Melanoma is the prototype of a tumor to which many forms of immunotherapy have been applied extensively over the past two decades. Melanoma vaccines (active specific immunotherapy) are designed to modulate the immune system and have subsequent anti-tumor effects with minimal toxicity. Previous attempts to produce melanoma vaccines include immunization with whole tumor cells/cell lysates admixed with nonspecific adjuvants. While these vaccines generate enhanced anti-tumor immunity in a subset of patients, some of whom survive for longer than historical controls, no clinical benefit has so far been demonstrated in a properly controlled phase III study. Genetic modifications of tumor cells to make them express cytokines afford new-generation melanoma vaccines, and generate long-lasting systemic antitumor immunity in animal models. Translation of these preclinical results primarily into melanoma patients with advanced diseases shows the potential to induce systemic antitumor immune responses and in some instances tumor regression with acceptably low toxicity. The efficacy of this novel vaccine approach would be expected to be higher when used in a postsurgical adjuvant setting when the tumor load is small. Other novel vaccine approaches such as dendritic cell-based therapy also hold promise for the treatment of melanoma. The clinical value of all these new approaches will eventually have to be established in prospectively randomized clinical studies.