Expression of Cancer/Testis Antigens CT10 and SSX in Multiple Myeloma: Promising Targets for Antigen-Specific Immunotherapy.

Background: The introduction of autologous and allogeneic stem cell transplantation has resulted in improved responses to treatment in patients with multiple myeloma (MM). However, despite high remission rates, recurrences are frequent due to remaining minimal residual disease. Myeloma-specific immunotherapies would represent a potentially useful treatment option in these patients. Cancer/testis (CT) antigens are highly attractive targets for T cell-mediated immunotherapy of cancer, due to their immunogenicity and restricted tissue expression. We investigated the expression of a larger number of CT antigens, the expression of which is characteristically restricted to cancer and normal testis, in patients with MM.

Methods: We analyzed the expression of 9 different CT antigens (SSX-1 to SSX-5, CT10/MAGE-E1, BAGE, MAGE-3, NY-ESO-1) in 10 myeloma cell lines, 54 bone marrow samples from patients with stage II-III myeloma (plasma cell infiltration 10–100 %), and 18 bone marrow samples from healthy donors using rtPCR.

Results: Myeloma cell lines showed a remarkably high expression of the majority of CT antigens. All antigens, with the exception of SSX-3, were expressed in 80–100% of cell lines. SSX-3 was not expressed in any cell line. Analyzing bone marrow samples from MM patients, we observed that CT10 showed a very high expression level with 55% of all malignant samples expressing this antigen. The SSX gene family evidenced high expression levels with 40% (SSX-1), 17% (SSX-2), 13% (SSX-4), and 15% (SSX-5) of patient samples expressing the given SSX family member. SSX-3 was not expressed in any samples. In agreement with previous findings we observed a high expression of MAGE-3 (61%), an intermediate expression of BAGE (18%), and a comparably low expression of NY-ESO-1 (7%). With the exception of SSX-4, which was expressed in 18% of healthy bone marrow samples, none of the CT antigens were expressed in non-malignant samples.

Conclusions: We show here for the first time that CT10 and members of the SSX gene family are strongly and specifically expressed in multiple myeloma. Importantly, both CT10 and SSX have been shown to elicit spontaneous immune responses in patients with solid tumors. Therefore, CT10 and SSX-1, SSX-2, and SSX-5 might represent valuable targets for antigen-specific immunotherapy of multiple myeloma.