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Melanoma Vaccines

The Potential for Clinical Efficacy with Minimal Toxicity in the Adjuvant Setting

  • Review Article
  • Published:
American Journal of Cancer

Abstract

While surgical therapy alone is successful in the treatment of early stage melanoma, the outcome remains poor for patients with high-risk melanoma (elther thick [>4mm] primary tumors or those with nodal metastases). Adjuvant chemotherapy has shown limited impact on survival, and while high-dose interferon has been reported to improve survival, treatment with interferon is not without significant toxicity. Based on evidence that the immune system may play a prominent role in melanoma, researchers have long hoped that immunotherapies would make a significant clinical impact in the treatment of melanoma. Melanoma vaccines have the potential of not only significant clinical efficacy, but minimal toxicity. As opposed to other adjuvant therapies, where we accept small gains in exchange for tremendous toxicity, the adverse effects of vaccines have been extremely limited, confined mostly to mild flu-like symptoms and reactions at the injection site.

Multiple approaches to melanoma vaccines have been investigated, each with advantages and drawbacks. Several types of vaccines attempt to target antigens commonly found on a majority of melanomas. Examples include ganglioside and peptide vaccines, anti-idiotype vaccines and allogeneic tumor cell vaccines. These vaccines have several advantages regarding cost and feasibility as they could be applied on a wide scale in the adjuvant setting; this would also allow the therapies to be effectively tested in multicenter trials. However, the available data raise concerns that these approaches may not generate a strong enough immune response in a large enough group of patients to make a significant impact.

An alternate approach is to use the patient’s own tumor to create a vaccine. Methods to accomplish this include both autologous cellular vaccines and dendritic cell vaccines. While these may be more immunogenic, the cost and technical demands may be prohibitive to using them in the adjuvant setting, where immunotherapies are most likely to be beneficial.

Despite our increased understanding of the immune system, and several decades of clinical trials, to date there has not been a large, randomized trial demonstrating an impact on survival with a melanoma vaccine. Several questions need to be addressed to help move this research in the right direction. We need to identify those factors that may determine which patient should receive which vaccine so that in the future, adjuvant treatments can be increasingly refined to the populations in which they are most likely to succeed. A better understanding of tumor immune escape mechanisms is necessary to develop new approaches to overcome them. Finally, it is important to identify more clinically relevant surrogate markers for the generation of an immune response in order to select which strategies show the most potential for success. The prospect of engendering lifelong immunity to a patient’s cancer with minimal toxicity is sufficiently realistic to justify the extensive research effort that is necessary to make this a reality.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Division of Surgical Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA

    Michael S. Sabel & Vernon K. Sondak

  2. MD 3304 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0932, USA

    Michael S. Sabel

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Correspondence to Michael S. Sabel.

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Sabel, M.S., Sondak, V.K. Melanoma Vaccines. Am J Cancer 3, 377–386 (2004). https://doi.org/10.2165/00024669-200403060-00005

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