SPECIFIC ACTIVATION OF RESTING T-CELLS AGAINST CA19-9-CELLS BY AN ANTI-CD3( TUMOR)CA19-9 BISPECIFIC ANTIBODY IN COMBINATION WITH A COSTIMULATORY ANTI-CD28 ANTIBODY/

Specific activation of resting lymphocytes for tumor targeting can be achieved by bispecific monoclonal antibodies (bi-mAb) with specificity for tumor antigens and T-cell-activating antigens, respectively, in c ombination with a costimulatory anti-CD28 antibody. We describe the ge neration and function of a bi-mAb with specificity for CD3 and for the tumor antigen CA19-9. The bi-mAb OKT3/NSI19-9 was generated by somati c fusion of two hybridoma lines secreting antibodies against CA19-9 an d CD3, respectively. A hybrid/hybridoma was established, and its bi-mA b was characterized. Ln combination with a costimulatory anti-CD28 mAb resting peripheral lymphocytes could be activated specifically with T -cell proliferation and secretion of high amounts of interferon-gamma. On specific T-cell activation, bi-mAb OKT3/NSI19-9 could also redirec t the cytotoxic effects of these T cells toward CA19-9+ tumor cells in vitro. Our results indicate that specific activation of resting T cel ls with bi-mAb OKT3/NSI19-9 in combination with an anti-CD28 mAb can a ctivate resting T cells specifically and leads to antigen-dependent bi -mAb-mediated cytotoxicity against CA19-9+ target cells. This approach may offer new perspectives for the specific immunotherapy of CA19-9tumors.