MONOCLONAL ANTINUCLEAR AUTOANTIBODY FROM THE AGED EFFECTIVELY SUPPRESSES TUMOR-DEVELOPMENT IN-VIVO

Serum anti-nuclear autoantibodies (ANA) are known to accumulate with n ormal disease-free aging. The functional role of such ANA remains uncl ear. We found that ANA-positive plasmas of aged Balb/c mice are reacti ve against the surface of tumor cell lines of different origin. The sa me dual specificity (against nucleochromatin and tumor cell surface) i s characteristic for monoclonal ANA 2C5 and 4D11 (both IgG,kappa) obta ined from two different fusions with splenocytes of aged ANA-positive Balb/c mice. In flow cytometric screening mAb 2C5 was reactive against the surface of many lymphoid and non-lymphoid tumor cell lines. of ro dent and human origin, but not against their normal counterparts. The interaction due to the artifact of in vitro cultivation or to Fc-FcR i nteraction was excluded. Tumor-suppressive function of mAb 2C5 was dem onstrated in in vivo experiments using mAb 2C5-reactive EL4 T lymphoma as a model. The development of this aggressive lymphoma was significa ntly suppressed by injections of mAb 2C5 (3 injections, 70 mu g each) even at relatively late stages, when macrometastatic disease was alrea dy present. The data lead us to a hypothesis on a beneficial role of A NA for the aged host.