Melanoma-associated antigen (MAGE)-A3 and MAGE-C2 are antigens encoded by cancer-germline genes, and have been recognized as potential prognostic biomarkers and attractive targets for immunotherapy in multiple types of cancer.
Here, we evaluated the safety and efficacy of an adoptive CD4<sup>+</sup> T-cell therapy using an MHC class II-restricted, HLA-DPB1*0401-restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3).
Clinical analysis of 223 primary patient-derived samples (ntumor = 161, nnormal = 62) showed a significant inverse correlation between MAGE-A3 promoter methylation and expression in the cancer samples (R = -0.63, p = 5.99e-19).
Expression of MAGE-A1-6 in sputum was identified in 57 of 119 patients (47.9%), and was independently correlated to double primary cancer (p = .024; odds ratio [OR] = 4.135).
Cancer/testis antigen MAGEC2, a member of the type I melanoma-associated antigen family, is expressed in a wide variety of cancer types but not in normal somatic cells.
The MAGE expression rates in cancer tissue and adjacent normal mucosa were 65.2%, 6.5% (<20 mm), 2.2% (20-50 mm) and 0.0% (>50 mm), respectively, while MAGE was not expressed in the mucosa of benign diseases.
The human melanoma-associated antigen family A (MAGE-A) has high specificity and expression in various malignancies, but individual family members are expressed at low frequency in any one particular type of cancer.