Malignant Melanoma Vaccine Therapy is Promising
By Barbara A. Biedrzycki, RN, MSN, AOCN, CRNP
Summary-Although there is no cure for malignant melanoma, there is hope through research into vaccine therapy, also known as active immunology. These cancer vaccines are therapeutic rather than prophylactic and have few or only mild side effects. Current studies show it is possible to obtain a vigorous immune response to cancer. Patient education in preventing and recognizing possible malignant skin lesions is vitally important to patient survival.
The idea of a vaccine to prevent melanoma is attracting considerable interest from potential consumers as well as researchers for two good reasons: There is no effective cure today for metastatic melanoma, and metastatic melanoma has proven very responsive to immunological changes. Melanoma most frequently occurs in the skin but also develops in mucosal surfaces or places where cells travel.1 Metastasis of primary melanoma spreads via the lymphatic system or hematological routes. Various treatments for metastatic melanoma include surgery, antineoplastic chemotherapy, immunotherapy, and radiation. Most patients receive more than one modality.
Early diagnosis and surgical treatment of primary melanoma smaller than 1.2 mm in thickness, classified by the Chicago-based American Joint Commission on Cancer (AJCC) as stage I, provide a 90% 10-year cure rate. The extreme importance of early detection of melanoma is demonstrated by comparing the highly favorable prognosis of AJCC stage I to the disheartening outlook for AJCC stage IV, melanoma that metastasizes to distant sites.
The mean survival of AJCC stage IV is only 4-8 months.2 The median age of melanoma occurrence is 53; however, there is a high incidence in the 25-29 age group.3 For the advanced practice nurse, these figures underscore the value of patient education, primary prevention, early detection, and prompt referrals to a dermatologist or surgeon when a suspicious lesion is identified. (See story above.)
Antineoplastic chemotherapy is cytotoxic, often killing cancer cells rapidly and providing a prompt response to therapy. Antineoplastic chemotherapy also induces various side effects, mild to severe.
How Vaccine Therapy Works
Vaccine therapy, known as active immunology, uses the patient's own immune system to fight cancer with a different approach. Unlike more familiar vaccines (such as tetanus, hepatitis B, and influenza), the cancer vaccine is therapeutic rather than prophylactic. It has no direct cytotoxic effect on cancer cells, and the delayed response usually appears months later. Vaccine therapy produces no or very mild side effects.
Cancer vaccines can be made from attenuated whole cells, cell walls, specific antigens, or nonpathogenic strains of living organisms. Early research used crude mixtures of whole or fragmented autologous or allogenic melanoma cells. Although unsuccessful at first, advances in molecular biology and immunology have identified many melanoma-associated antigens (MAA) that can induce immune responses in melanoma patients.
Outcomes measures in melanoma vaccine research are determined by quantifying the induction of humoral antibodies and the development of cell-mediated responses to the MAA. MAA is manipulated genetically and/or enhanced by adding carriers, immune stimulants, or antigens targeting the delivery to particular cells or organ sites. Cancer vaccines stimulate the immune system to destroy cancer cells and overcome the tumor-derived immunosuppression.
Approach Uses Cloned Genes
Rosenberg et al at the National Cancer Institute (NCI) discovered a new approach to vaccine therapy when they observed promising results with cloned genes encoding cancer antigens.4 Rosenberg et al started with a specific MAA, the gp100 molecule, specifically its epitope g209-217. They modified the g209-217 peptide to a new substance, g209-2M. The synthetic peptide g209-2M bound to the HLA-A2 molecule (a common immune system marker that allows distinction between self and nonself in stimulating an immune response) with greater affinity than the unmodified peptide and with an increased ability to generate melanoma-reactive cytotoxic T lymphocytes (CTLs) in vitro.
Since there was a response in vitro, Rosenberg et al set out to determine the potential effects of their creation on metastatic melanoma in humans. Fifty-one patients with metastatic melanoma participated in this study, which included three sequential trials. Each patient had undergone prior surgery, and most had previous chemotherapy, radiotherapy, or immunotherapy, including interleukin-2 (IL-2). Eighty-two percent reported receiving two modalities.
Three Trials Conducted
The first trial of nine patients received the unmodified peptide g209-217. One patient experienced an objective cancer response that lasted four months. The second group of 11 patients received the synthetic peptide g209-2M with no objective cancer regression.
The third group, 31 patients, received the synthetic peptide g209-2M with IL-2 concomitantly throughout the treatment or concomitantly after two cycles of g209-2M peptide. To prevent side effects from IL-2, all patients received acetaminophen, rantidine, and indomethacin.
Eight (42%) of 19 patients receiving IL-2 concomitantly with the g209-2M peptide demonstrated objective cancer regression. Five (42%) patients receiving IL-2 concomitantly with the g209-2M peptide after two cycles without IL-2 showed objective cancer regression.
Objective Response Rate of 42%
Rosenberg et al, noting that previous studies using high-dose IL-2 alone in 62 melanoma patients had a 15% response rate, said, "Although the dangers of comparison with retrospective or simultaneous nonrandomized patient groups are well-appreciated, the 42% objective response rate we have seen . . . is substantially higher than . . . using IL-2 alone." In a National Institutes of Health press release, Steven Rosenberg, principal investigator and chief of surgery at NCI, said, "This present study shows that it is possible to stimulate a vigorous immune response even when the patients have a heavy tumor burden."5
References
1. Groenwald S, Frogge M, Goodman M, Yarbro C. Cancer Nursing: Principles and Practice. Sudbury, MA: Jones and Bartlett Publishers; 1993.
2. Morton D, Barth A. Vaccine therapy for malignant melanoma. CA Cancer J Clin 1996;46:225-241.
3. Dunn S. Primary Care Consultant. St. Louis: Mosby; 1998:362-363.
4. Rosenberg S, Yang J, Schwartzentruber D, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with meta static melanoma. Nature Medicine 1998;4:321-327.
5. National Institutes of Health press release. Synthetic peptide vaccine for melanoma holds promise. March 2, 1998.
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