Vaccine Therapy for Melanoma

Introduction

Vaccination aimed at reducing the incidence of certain infectious diseases has led to vast improvements in health care. Substantial research has been directed toward the development of vaccine therapy for the treatment of cancer, and melanoma has been an attractive target. Advanced melanoma is a disease with high cancer-specific mortality and few effective treatment options. Traditional treatment modalities such as chemotherapy and radiation have limited utility in the treatment of advanced melanoma, but it has been observed, albeit in isolated cases, that immune mechanisms can slow the progression of melanoma and even cause regression of established melanoma metastases ( Fig. 54.1 ). In addition, tumor-reactive T cells can be measured in the peripheral blood as well as within the resected tumors of melanoma patients. When recovered from patients, these T cells are able to respond to melanoma antigens derived from the same patient in vitro.

Preclinical studies such as these have spurred interest in the development of vaccine therapy for the treatment of melanoma. In general terms, this involves the provision of antigens to patients in order to engender an anti-tumor immune response and eventual regression of disease. This chapter will review the different types of anti-melanoma vaccines that have been developed, the past successes and failures of vaccine therapy in clinical trials, as well as future directions that are being explored to improve the efficacy of vaccine therapy for melanoma.

Requirements for an effective anti-melanoma vaccine

In order for a vaccine to be effective in treating melanoma, several conditions must be satisfied. First, the vaccine must contain antigens that are sufficient to induce a specific immune response when administered to patients. Second, these target antigens must be expressed on the tumor in order for the vaccine to induce an effective anti-tumor immune response. Third, the vaccine must be safe; it must generate a long-lasting tumor-specific immune response without causing significant autoimmunity or inducing a tolerant state that could actually promote tumor growth. Finally, the vaccine must be amenable to large-scale production in a uniform fashion in order for it to be feasible to administer on a large scale. The above requirements must all be taken into consideration when designing an anti-melanoma vaccine.