Aetna considers melanoma vaccine (also known as Theraccine vaccine or Oncophage vaccine) experimental and investigational for any indication.

Melanoma vaccine is prepared from melanoma cell lines that are cultured in vitro.  The vaccine product is designed to contain one or more antigens that are unique to melanoma cells; some preparations also contain "adjuvants" (such as BCG) thought to enhance immunogenicity of the preparation.

Currently, no melanoma vaccine products are licensed for marketing in the United States.  Until a commercial preparation is available, there is significant potential for variability between products and batches.  Effects that are seen in patients to whom these products are administered may be due to the components thought to be active, or to other components which are contaminants, adjuvants or excipients.  In those studies lacking a concurrent control group, it is impossible to distinguish which components are active.  Ribi Immunochem Research has developed a standardized melanoma vaccine called Melacine.  As a biological, this product would be evaluated and licensed by the Center for Biological Evaluation and Research of the Food and Drug Administration.  At this time, no application for licensure has been filed for this product.

Several published studies have suggested that melanoma vaccine may be effective in the treatment of malignant melanoma and/or prevention of metastasis of melanoma; however, these studies are not adequate to establish the safety and/or efficacy of this therapy.  In addition, there have been a number of reports of Phase I and Phase II studies that have demonstrated increases in tumor-specific cytotoxic T lymphocytes and other immune responses in patients vaccinated with various melanoma vaccines.  A number of these studies have incorporated interleukin-2 and other adjuvants to improve immune response to melanoma vaccine.  The second interim report from a Phase III, multicenter randomized controlled clinical trial of a melanoma vaccine, however, showed no significant overall survival benefit in vaccinated melanoma patients.  A retrospective analysis of clinical trial results identified subsets of patients that appeared to have improved survival with the vaccine; this retrospective analysis suggests that a vaccine may be effective in selected subgroups of melanoma patients.

Randomized controlled clinical trials, where subgroups of patients are identified prospectively, are necessary to confirm the efficacy of melanoma vaccine in selected patient subgroups. Kuhn and Hanke (1997) concluded in a recent review of the current status of melanoma vaccines that "[t]he clinical effectiveness of melanoma vaccines is unclear and adequately controlled studies need yet to be performed".  A former President of the American Cancer Society stated that "[t]he success of melanoma vaccines has been inhibited by the large number of potential antigen targets on the melanoma cell, which may vary from tumor to tumor. In addition, the lack of intermediate end points for assessment of the effect of immunotherapy has impeded research in this field."

The U.S. Food and Drug Administration (FDA) has deemed the Antigenics Inc. (New York, NY) Oncophage late-stage investigational cancer vaccine an orphan drug for metastatic melanoma. The FDA orphan drug designation was designed to encourage the development of therapies for conditions affecting fewer than 200,000 people in the United States.  The designation entitles the sponsor to aid with the development program, tax breaks, waivers from certain regulatory fees and 7 years of additional marketing exclusivity if the product eventually is approved.

The Oncophage vaccine is prepared by removing a tumor from the patient and isolate specific antigens of the particular cancer.  The vaccine is composed of heat-shock proteins that are bound to other proteins specific to tumor antigens.  According to Antigenics, Inc., studies have shown that the protein complex, when purified from tumor cells and reintroduced to the patient, appears to stimulate cellular immunity.  The immune response appears to be directed specifically to cancer cells, leaving the patient's healthy tissue intact.  In May 2002, Antigenics reported that it had begun enrolling patients in the United States and Europe in a pivotal phase III trial of Oncophage for stage IV metastatic melanoma.

Elliott and Dalgleish (2004) stated that melanoma vaccines offer new hope to patients with metastatic melanoma, although convincing survival advantages have yet to be reported.  Bystryn and Reynolds (2005) stated that vaccines are a promising but still experimental treatment for melanoma.

Guidelines on malignant melanoma from the National Institute for Health and Clinical Excellence (2006) have concluded that "[v]accine therapy for advanced [malignant melanoma] remains uncertain and its use should only be in the context of a clinical trial." A systematic evidence review in BMJ Clinical Evidence (Savage, 2006) concluded that adjuvant vaccines in people with malignant melanoma are of "unknown effectiveness."

Lens and colleagues (2008) assessed different vaccines tested in stage III and/or IV melanoma patients.  Systematic review of the published evidence on vaccine therapy in melanoma was carried out.  Melanoma vaccines can be classified into 6 groups: (i) whole-cell vaccines, (ii) dendritic cell vaccines, (iii) peptide vaccines, (iv) ganglioside vaccines, (v) DNA vaccines and (vi) viral vectors.  The main characteristics of these vaccines including their advantages and disadvantages and the results from conducted trials were presented.  Clinical responses to melanoma vaccines are still poor and currently there is no melanoma vaccine with a proven efficacy.  The authors concluded that vaccine therapy still remains an experimental therapy in patients with metastatic melanoma.  Further research is needed although a future therapy for advanced melanoma is probably a multi-modal approach including vaccines, adjuvants and negative co-stimulatory blockade.  This is in agreement with the observations of Stein and Brownell (2008) who noted that advanced melanoma has a poor prognosis, and standard adjuvant treatment offers little survival advantage.  Current efforts are aimed at combining chemotherapy and novel immunomodulators, which include vaccines, cytokines, and anti-CTLA4 antibodies.  Hundreds of combination therapies are currently undergoing clinical trials.  All advanced melanoma patients should be considered for enrollment in a trial for their own benefit as well as for the advancement of melanoma treatment.  Thus far, no single investigative approach stands out as highly effective, however, they all hold promise with rare patients showing durable responses.  Most treatment protocols are evaluating combinations of adjuvant therapies, hoping to achieve a synergistic effect.

Lesterhuis and associates (2008) stated that dendritic cells are the directors of the immune system, capable of inducing tumor antigen-specific T- and B-cell responses.  As such, they are currently applied in clinical studies in cancer patients.  Early small clinical trials showed promising results, with frequent induction of anti-cancer immune reactivity and clinical responses.  In recent years, additional trials have been carried out in melanoma patients, and although immunological responses are often reported, objective clinical responses remain anecdotal with objective response rates not exceeding 5 to 10 %. Thus, dendritic cells vaccination research has now entered a stage in between "proof of principle" and "proof of efficacy" trials.  Crucial questions to answer at this moment are why the clinical responses remain scarce and what can be done to improve the efficacy of vaccination.