Seroreactivity against MAGE-A and LAGE-1 proteins in melanoma patients.
BACKGROUND
Cancer-testis antigens exemplify a growing number of tumour antigens which are expressed in a variety of malignancies, but not in normal tissues other than germ cells, primarily those of the testis.


OBJECTIVE
To investigate the humoral response to known cancer-testis antigens in melanoma patients.


METHODS
We used phage clones coding for seven different melanoma antigens MAGE-A or LAGE-1A proteins. These clones were isolated using the newly developed DNA hybridization analysis of recombinantly expressed cDNA libraries (HYREX) approach. HYREX combines the advantage of a nonradioactive library screening method with the possibility of subsequently analysing the serological response to the recombinant proteins. We isolated clones coding for MAGE-A1, -A3, -A4b, -A6, -A9 and -A12, as well as LAGE-1A. Additionally, we correlated gene expression and seroreactivity.


RESULTS
Between 13% and 27% of sera (n = 15) were reactive against individual tumour antigens. We found the presence of specific antibodies was, with only two exceptions, generally correlated with mRNA expression of the antigen within cell lines derived from the same patient. While cross-reactivity of patients' IgG might play a role in these cases, antibodies from patients' sera were able to distinguish even the closely related MAGE-A3 and -A6. In general, the mRNA expression frequency was higher than the detected IgG responses.


CONCLUSIONS
Antibody recognition of specific tumour antigens by patients' sera may be used for evaluating the possible immunogenicity of new antigens; serological tests could be used for tumour monitoring purposes.
Usener
D
D
Skin Cancer Unit, D070, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Gerhardt
A
A
Schadendorf
D
D
Eichmüller
S
S
D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D011506:Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins