Original Article

Journal of Investigative Dermatology (1998) 111, 1034–1039; doi:10.1046/j.1523-1747.1998.00411.x

Anti-Tyrosinase-Related Protein-2 Immune Response in Vitiligo Patients and Melanoma Patients Receiving Active-Specific Immunotherapy

Tetsuro Okamoto, Reiko F Irie*, Shigeyuki Fujii, Sharon K S Huang, Anne J Nizze, Donald L Morton and Dave S B Hoon

  1. Department of Molecular Oncology Santa Monica, California, U.S.A
  2. *Department of Biotechnology Santa Monica, California, U.S.A
  3. John Wayne Cancer Clinic, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California, U.S.A

Correspondence: Dr Dave S. B. Hoon, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404

Received 22 April 1998; Revised 18 June 1998; Accepted 29 July 1998.

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Abstract

Several melanosome glycoproteins have been shown to be antigenic in humans. Correlation of antigen-specific immune responses in patients with the autoimmune disease vitiligo, therapy-induced hypopigmentation, and cutaneous melanoma has not been well studied. We examined antibody responses to a melanocyte autoantigen, tyrosinase-related protein-2 (TRP-2), as it is highly expressed in cutaneous melanoma and melanocytes. TRP-2 recombinant protein was synthesized for western blot and affinity anti-TRP-2 enzyme-linked immunosorbent assay. We demonstrated that patients with malignant melanoma, vitiligo, and active-specific immunotherapy-induced depigmentation had significant anti-TRP-2 IgG titers. The highest level of anti-TRP-2 IgG response was found in vitiligo patients. Induction and enhancement of anti-TRP-2 IgG responses were observed in melanoma patients treated with a polyvalent melanoma cell vaccine containing TRP-2. Active-specific immunotherapy could induce and/or augment the TRP-2 IgG antibody titers. Melanoma patients who developed hypopigmentation and had improved survival after polyvalent melanoma cell vaccine had significantly augmented anti-TRP-2 antibody responses compared with patients with poor prognosis. This study demonstrates that TRP-2 autoantigen is immunogenic in humans. TRP-2 antibody responses provide a linkage between autoimmune responses by vitiligo patients and melanoma patients responding to immunotherapy who have induced hypopigmentation.

Keywords:

autoantibodies, autoimmunity, human-clinical studies, tumor immunity

Abbreviations:

MAA, melanoma-associated antigen; MAH, melanoma-associated hypopigmentation; PMCV, polyvalent melanoma cell vaccine; TRP-1,2, tyrosinase-related protein 1 and 2

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