NY-ESO-1 Specific Antibodies Are Frequently Detected in Hight-Risk Myeloma.

We have previously reported that NY-ESO-1 is especially present in high-risk multiple myeloma (MM) as defined by abnormal metaphase cytogenetics. The presence of NY-ESO1 specific antibody (ab) response is an excellent surrogate marker for the presence of a CD4⁺ NY-ESO-1 specific T-cell response, which is essential to priming, expanding and sustaining CD8⁺ NY-ESO-1 specific T-cell responses. We therefore studied the sera of 56 MM patients enrolled in our Total Therapy II protocol for the presence of specific NY-ESO-1 ab by sandwich ELISA using highly purified recombinant NY-ESO-1 protein. NY-ESO-1 RNA expression of purified MM cells was determined by gene expression profiling. NY-ESO-1 specific ab were detected in 13/39 (33%) of patients with NY-ESO-1 positive MM. In contrast, patients with NY-ESO-1 negative MM (n=27) all tested negative for NY-ESO-1 ab by ELISA, as did normal donors (n=20). Antibodies to NY-ESO-1 were present in 9/19 (47.3%) of patients who were studied with frank, NY-ESO-1 positive MM (at diagnosis, progressive disease or at relapse). All patients with progressive/relapsed MM had previously received intensive chemotherapy and/or auto-transplantation. In NY-ESO-1 positive MM patients who had a very good partial or partial response to therapy NY-ESO-1 specific ab were detected in only 4 patients of 13 tested (30.7%). In contrast, no NY-ESO-1 specific ab were detected in 7 NY-ESO-1 positive MM patients who had achieved (near) complete remission. Nine of the 13 (70%) NY-ESO-1 ab positive patients had high-risk MM as defined by abnormal metaphase cytogenetics. We conclude that the presence of NY-ESO-1 positive MM, and thus antigenic stimulation, is the principal determinant of the ability to mount a humoral response to NY-ESO-1 protein despite the presence of an immune system compromised by the immunosuppressive effects of MM or (high dose) chemotherapy. Further, NY-ESO-1 specific ab are principally found in patients with high-risk MM. The presence of spontaneous humoral immune responses to NY-ESO-1 is important since it suggests that there is a reservoir of NY-ESO-1 specific CD4⁺ T-cells that could be expanded and utilized for the immunotherapy of high-risk MM by vaccinating with NY-ESO-1 peptides, proteins or DNA based vaccines.