Tumor vaccines: a role in preventing recurrence in melanoma?

Patients presenting with thick primary melanomas or those with regional nodal metastases have a high risk of recurrence after surgery alone. Chemotherapy has limited efficacy in the adjuvant setting, and while the use of high-dose interferon in the adjuvant setting has been reported to improve survival, treatment with interferon is not without significant cost and toxicity. Mounting evidence suggests a prominent role for the immune system in the natural history of melanoma, and the clinical success of interferon highlights the potential for immunotherapy to prevent recurrence. Many researchers hope to use melanoma vaccines to reduce recurrence without significant toxicity, and many different vaccine strategies are under investigation. Peptide vaccines attempt to induce immunity to melanoma MHC-restricted peptide antigens by delivering the peptide to the patient along with an immune adjuvant meant to induce inflammation and stimulate immunity. While peptide vaccines have advantages with regard to cost and feasibility, it is still unclear whether highly purified peptides will stimulate an adequate immune response. An alternative approach is the use of cellular vaccines. Autologous cellular vaccines present all biologically relevant antigens to the immune system, but this is limited to individuals with sufficient tumor to prepare a vaccine. Allogeneic cellular vaccines are based on the fact that melanoma-associated antigens are shared among a large number of patients, so a vaccine prepared from a cultured cell line could stimulate an anti-tumor immune response in many patients. Allogeneic vaccines are available for all patients, and can be standardized, preserved and distributed in a manner akin to any other therapeutic agent. Because of this, they are more readily available for evaluation in large trials, and there are two major allogeneic vaccines presently being evaluated as an adjuvant therapy for melanoma. Several additional approaches to vaccine therapies are being investigated including among others ganglioside vaccines, viral oncolysates, cytokine gene-modified tumor cell vaccines, dendritic cell vaccines, anti-idiotype antibodies and DNA vaccines. While there appears to be tremendous potential for vaccines, it must be remembered that there has been significant interest in immunotherapy for melanoma for over 50 years and, to date, no large prospective, randomized trial has shown a survival benefit.