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Background: In the development of an antimelanoma vaccine, a critical factor is the identification of antigens that induce a strong immune response in humans and that are expressed by melanoma cells in vivo. The aim of this study was to identify candidate antigens for such vaccine. Methods: Sixty-nine patients with surgically resected melanomas (American Joint Commission on Cancer [AJCC] stage III) were immunized with a polyvalent vaccine containing multiple melanoma antigens. Antimelanoma antibodies generated in the patients' sera were used as probes to identify the melanoma antigens that are immunogenic in humans and that are expressed on the tumor tissue in vivo. Such responses were determined by an immunoblotting assay that employed an antigen source prepared from membrane fractions of freshly excised melanoma tissue. Results and Conclusions: Vaccine treatment stimulated antibody responses in 35 (51%; 95% confidence interval [CI] = 39%-63%) of 69 sequentially enrolled patients. The antibodies were directed to one or more antigens with molecular masses of 45, 59, 68, 79, 89, 95, and/or 110 kd. The most immunogenic antigens were p110 and p68, which induced responses in 33% (95% CI = 22%-44%) and 25% (95% CI = 15%-35%) of patients, respectively. Both antigens were commonly expressed on different melanomas, but they were absent on autologous normal tissue and on an unrelated allogeneic tumor. All the above antigens are attractive candidates for vaccine construction. [J Natl Cancer Inst 1998;90: 146-9]

Background. Melanoma vaccine treatment appears to slow the progression of melanoma in some patients, particularly in patients in whom it stimulates cellular antimelanoma immune responses. The relationship of vaccine-induced antibody responses to clinical outcome is less clear. The purpose of this study was to investigate the clinical relevance of antibody responses to melanoma vaccine immunization. Methods. Eighty-two evaluable patients with surgically resected American Joint Committee on Cancer Stage III malignant melanoma were immunized to a partially purified, polyvalent, melanoma antigen vaccine. Antimelanoma antibodies were measured by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis before vaccine treatment and 1 week after the fourth immunization. Results. Vaccine treatment induced or augmented antibody responses to melanoma in 32 (39%) of the patients. The antibodies were directed to one or more antigens of 38-43, 75, 110, 150 and/or 210 kDs, which previously have been shown to be expressed preferentially in cultured human melanoma cells. The median disease free survival of patients with a vaccine-induced antibody response to one or more of these antigens was 5.4 years compared with 1.4 years for nonresponders (P = 0.06), and 5-year overall survival was 71% compared with 44%, respectively (P = Conclusions. The antibody response to vaccine treatment is an immune marker of vaccine activity that appears to be predictive of a later reduction in the recurrence of melanoma and is unrelated to the vaccine's ability to induce cellular immune responses. This finding suggests that vaccine treatment may be effective in slowing the progression of melanoma in some patients and that the protective effect is mediated partly by vaccineinduced antimelanoma antibodies.

The authors investigated whether there was a relationship between the induction of a delayed-type hypersensitivity (DTH) response to melanoma vaccine immunization and disease recurrence. They studied prospectively 94 evaluable patients with surgically resected Stage II malignant melanoma who were immunized to a partially purified, polyvalent, melanoma antigen vaccine. The DTH response to skin tests to the vaccine was measured before treatment and at the fourth vaccine immunization. Vaccine treatment induced a strong DTH response in 29 (31%) patients, an intermediate response in 24 (25%), and no response in 41 (44%). The median disease-free survival (DFS) of patients with a strong, intermediate, and no DTH response to vaccine immunization was more than 72 months, 24 months, and 15 months, respectively. The relationship between an increase in the DTH response and a prolonged DFS was statistically significant (P = 0.02); clinically meaningful (the median DFS of patients with a strong DTH response was 4.7 years longer than that of nonresponders); and, by multivariate analysis, independent of disease severity or overall immune competence. These findings suggest, but do not prove, that vaccine treatment can slow the progression of melanoma in some patients. Cancer 1992; 69:1157-1164.

Pemphigus is a very serious skin disease characterized by large blisters which break easily, leaving raw patches; the patient becomes weak and susceptible to major infection. Pemphigus is usually treated with high doses of corticosteroids and immunosuppressive agents, to moderate the immune response. The adverse effects of corticosteroids have prompted a search for other forms of therapy. One suggested method of treatment is plasmapheresis, a procedure in which the blood is removed from the patient, and the plasma, containing pemphigus antibodies, is separated from the cellular matter of the blood and discarded. The cellular matter, supplemented with salt solution and albumin, is then returned to the patient. In order to test the effectiveness of this method of treatment, eleven patients were treated with a regimen of plasmapheresis, accompanied by corticosteroids and immunosuppressive drugs, while a control group of eleven patients were treated with the corticosteroids and immunosuppressive drugs only. At the beginning of the treatment, the pemphigus antibody levels in both patients were approximately the same. Three weeks after hospitalization and treatment, the patients receiving plasmapheresis showed an 82 percent decrease in pemphigus antibodies, compared with the control group, who showed an 18 percent reduction. The study demonstrated the ability of plasmapheresis, in conjunction with corticosteroids and immunosuppressive drugs, to reduce levels of pemphigus antibodies rapidly. Treatment must be intense, since the removal of the antibodies must be at a rate that surpasses the rate of creation of new antibodies. New antibody production can be inhibited by immunosuppressive drugs and prednisone. Continuous monitoring is necessary to assure that newly created antibodies are not replacing those removed. The procedure is not effective in some patients who produce new antibodies rapidly. (Consumer Summary produced by Reliance Medical Information, Inc.)