Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation

Background

Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer–testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM.

Methods

Frequency and characteristics of antibody responses against cancer–testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients.

Results

We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2^85–90.

Conclusions

We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.

     

Temporal and regional trends of cancer mortality in West Germany

Age-specific and cumulative mortality rates are presented for different cancer sites from 1970 until 1988 for the 11 individual federal states of West Germany (FRG). Sex- and age-specific evaluations are performed and tempora and regional trends in mortality from different cancer sites are revealed. In the FRG there is no comprehensive cancer registry with national coverage for recording cancer patients of all ages (nationwide incidence rates are available only for childhood cancers). Therefore, in view of the lack of a nationwide cancer registry the importance of long-term cancer mortality studies for health policy is emphasized. Methodological aspects of certification regulations and classification of cancer sites are discussed.