Melanocyte differentiation antigen RAB38/NY-MEL-1 induces frequent antibody responses exclusively in melanoma patients.
Expression pattern and immunogenicity are critical issues that define tumor antigens as diagnostic markers and potential targets for immunotherapy. The development of SEREX (serological analysis of recombinant expression libraries) has provided substantial progress in the identification of tumor antigens eliciting both cellular and humoral immune responses in cancer patients. By SEREX, we have previously identified RAB38/NY-MEL-1 as a melanocyte differentiation antigen that is highly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types. In this study, we further demonstrate that RAB38/NY-MEL-1 is strongly immunogenic, leading to spontaneous antibody responses in a significant proportion of melanoma patients. The immune response occurs solely in malignant melanoma patients and was not detected in patients with other diseases, such as vitiligo, affecting melanocytes. Fine analysis of the spontaneous anti-RAB38/NY-MEL-1 antibody response reveals a polyclonal B cell recognition targeting various epitopes, although a dominant immunogenic region was preferentially recognized. Interestingly, our data indicate that this recognition is not rigid in the course of a patient's response, as the dominant epitope changes during the disease evolution. Implications for the understanding of spontaneous humoral immune responses are discussed.
Zippelius
Alfred
A
Klinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland. alfred.zippelius@usz.ch
Gati
Asma
A
Bartnick
Tammo
T
Walton
Senta
S
Odermatt
Bernhard
B
Jaeger
Elke
E
Dummer
Reinhold
R
Urosevic
Mirjana
M
Filonenko
Valeriy
V
Osanai
Kazuhiro
K
Moch
Holger
H
Chen
Yao-Tseng
YT
Old
Lloyd J
LJ
Knuth
Alexander
A
Jaeger
Dirk
D
D000912:Antibodies, Neoplasm / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D007150:Immunohistochemistry; D008545:Melanoma / Q000097:blood / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000276:immunology*
D000912:Antibodies, Neoplasm; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; C412058:RAB38 protein, human; D020691:rab GTP-Binding Proteins