Antibody response against cancer-testis antigens MAGEA4 and MAGEA10 in patients with melanoma

Abstract

Melanoma-associated antigen A (MAGEA) represent a class of tumor antigens that are expressed in a variety of malignant tumors, however, their expression in healthy normal tissues is restricted to germ cells of testis, fetal ovary and placenta. The restricted expression and immunogenicity of these antigens make them ideal targets for immunotherapy in human cancer. In the present study the presence of naturally occurring antibodies against two MAGEA subfamily proteins, MAGEA4 and MAGEA10, was analyzed in patients with melanoma at different stages of disease. Results indicated that the anti-MAGEA4/MAGEA10 immune response in melanoma patients was heterogeneous, with only ~8% of patients having a strong response. Comparing the number of strongly responding patients between different stages of disease revealed that the highest number of strong responses was detected among stage II melanoma patients. These findings support the model that the immune system is involved in the control of melanoma in the early stages of disease.

Keywords: antibodies; cancer; cancer-testis antigens; melanoma; melanoma antigens.

Figure 1.

Antibody response against MAGEA4 and MAGEA10 proteins in melanoma patients and controls. A comparison of the magnitude of the anti-MAGEA4 and anti-MAGEA10 immune responses of blood bank controls vs. melanoma patients (stages 0–IV combined) by Tukey box plots showing median and interquartile ranges. Dots correspond to individual blood bank controls and patients. The Y-axis denotes optical density values obtained from the ELISA assay. The number of sera is shown in the parentheses. MAGEA, melanoma-associated antigen A.

Figure 2.

A subgroup analysis of the magnitude of the anti-MAGEA4 and anti-MAGEA10 immune responses of melanoma patients (stages 0–IV). Tukey box plots with median and interquartile ranges are shown, as well as dots corresponding to individual blood bank controls and patients. The Y-axis denotes optical density values at 495 nm. The number of sera is shown in the parenthesis. MAGEA, melanoma-associated antigen A.

Figure 3.

Comparison of OD values of MAGEA4 and MAGEA10 among the strongly responding patients. Lines correspond to mean values of ELISA assay for MAGEA4 (blue) and MAGEA10 (orange), respectively. Error bars show the SD of at least three different experiments performed on separate ELISA plates. MAGEA, melanoma-associated antigen A.

Figure 4.

The fraction of strongly responding patients in relation to the melanoma stage. Patients with OD values higher than the mean OD of the healthy blood bank donors plus 2 SD-s are included. The number of sera is shown in the parenthesis. MAGEA, melanoma-associated antigen A.

Figure 5.

ROC curve for anti-MAGE antibody detection. Antibody levels among 185 melanoma patients and 43 blood bank controls were determined by ELISA. The AUC value was 0.74. ROC, receiver operating characteristic; MAGE, melanoma-associated antigen; AUC, area under the curve.