| Research Summary |
| Immune mechanisms play a critical role in several diseases involving pigment cells, including: 1) malignant melanoma, in which anti-pigment cell immune responses can increase resistance to this cancer; 2) vitiligo, which is associated with autoantibodies to melanocytes; and 3) alopecia areata, which is also associated with an abnormal immune response to hair follicle-specific melanocytes. We concentrate on humoral and cellular immune responses to pigment cells to define the pathogenesis of these diseases and, ultimately, to develop improved treatments with our major efforts toward developing a vaccine for malignant melanoma. We have constructed a partially purified, polyvalent melanoma antigen vaccine prepared from shed antigens. In clinical trials for several years, vaccine results are very promising. As illustrated below, a striking relation exists between the vaccine's ability to immune responses to melanoma and improved clinical outcome, suggesting strongly that the vaccine is clinically effective. Current projects include: 1) conducting a phase III randomized clinical trial to establish the clinical effectiveness of the vaccine; 2) conducting several phase I and II clinical trials to develop procedures that increase the potency of the vaccine; 3) developing new assays to measure HLA-restricted CD4+, CD8+, and other T-cell responses induced by vaccine treatment; 4) identifying and characterizing melanoma antigens which are immunogenic in humans and which would be good candidates for constructing second generation vaccines; and 5) identifying vaccine-induced immune mechanisms which are important in mediating tumor-protective immunity. Regarding vitiligo, we are investigating autoantibody and cellular immune responses to pigment cells which are associated with the disease and the role they may play in pathogenesis. Similar studies are ongoing in alopecia areata. Relation between cellular response to melanoma vaccine treatment and survival in AJCC stage III melanoma Increase in cellular responseaPts n=94Duration of median survival - Disease-freebDuration of median survival - Overallc None4115 mo44 mo Weak2424 mo57 mo Strong29>72 mo>89 mo a Increase in induration of delayed-type hypersensitivity responses over baseline in same patient b Median survival from surgical treatment of stage II disease to recurrence c Median from surgical treatment of stage II disease to death
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| Research Information |
Research Interests | Melanoma , Skin Cancer, Prostate Cancer, Vaccines, Immune Mechanisms in Pigment Cell Diseases
| Research Keywords | melanoma, skin cancer,vaccines, prostate cancer, alopecia areata, melanocytes, vitiligo, blistering diseases,
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