The Cancer/Testis Antigens of SSX4, MAGE-A3, and CTAG2 Are Attractive Targets for Cancer Immunotherapy in Korean Patients with Multiple Myeloma

Introduction: Cancer/testis antigens (CTAs) are an attractive target for cancer immunotherapy because of a tumor-restricted expression and remarkable immunogenicity. Several CTAs have been used as a source of tumor antigen in dendritic cell therapy against multiple myeloma (MM), but there was no report the CTAs in Asian patients with MM. In this study, we evaluate the expression of 10 CTAs on malignant plasma cells of bone marrow in 18 Korean patients with relapsed or refractory MM.

Materials and methods: Eighteen patients with relapsed or refractory MM were classified as four categories according to paraprotein subtypes: IgG (n=7), IgA (n=5), light chain-lambda (n=3), and light chain-kappa (n=3). The expression pattern of 10 CTAs, including NY-ESO-1, SSX2, SSX4, SSX5, MAGE-A3, MAGE-C1, MAGE-C2, BAGE2, CTAG2, and SPA7, was studied by real-time quantitative polymerase chain reaction in CD138⁺ cells of BM mononuclear cells (MNCs) obtained from MM patients. In addition, we compared it with expression pattern of CTAs in the MNCs from healthy normal donors and the CD138^- cells of BM MNCs from MM patients as controls.

Results: In CD138⁺ cells of BM MNCs from the patients, five CTAs, including SSX2, SSX4, MAGE-A3, MAGEC2, and CTAG2, showed high frequency and overall 5.4 to 63.9 fold increase expression in the quantitative mRNA survey compared to MNCs from healthy donors and CD138^- cells of BM MNCs from patients. Expression pattern of 5 CTAs was slightly different by paraprotein subtypes: IgA subtype - SSX4 (17.1 fold increase), MAGE-A3 (11.0 fold increase), and CTAG2 (5.9 fold increase); IgG subtype - CTAG2 (63.9 fold increase), SSX4 (40.2 fold increase), and MAGE-A3 (39.9 fold increase); lambda light chain subtype - CTAG2 (42.4 fold increase), SSX4 (29.0 fold increase), and MAGE-A3 (24.4 fold increase); kappa light chain subtype - SSX2 (6.4 fold increase), MAGE-C2 (6.2 fold increase), MAGE-A3 (5.4 fold increase), and SSX4 (5.4 fold increase).

Conclusion: This study suggests that three CTAs, such as SSX4, MAGE-A3, and CTAG2, highly expressed on malignant plasma cells are potentially promising targets for cancer immunotherapy in Korean patients with relapsed or refractory MM.