The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells

Bispecific antibodies (bsAb) are considered as promising tools for the elim ination of disseminated tumour cells in a minimal residual disease situatio n. The bsAb-mediated recruitment of an immune effector cell in close vicini ty of a tumour cell is thought to induce an antitumoural immune response. H owever, classical bispecific molecules activate only a single class of immu ne effector cell that may not yield optimal immune responses. We therefore constructed an intact bispecific antibody, BiUII (anti-CDS x anti-EpCAM), t hat not only recognizes tumour cells and T lymphocytes with its two binding arms, but also binds and activates Fc gamma-receptor positive accessory ce lls through its Fc-region. We have demonstrated recently that activated acc essory cells contribute to the bsAb-induced antitumoural activity. We now a nalyse this stimulation in more detail and demonstrate here the BiUII-induc ed upregulation of activation markers like CD83 and CD95 on accessory cells and the induction of neopterin and biopterin synthesis. Experiments with p ure cell subpopulations revealed binding of BiUII to CD64+ accessory cells and CD16+ NK cells, but not to CD32+ B lymphocytes. We provide further evid ence for the importance of the Fc-region in that this bispecific molecule s timulates Fc gamma-R-positive accessory cells to eliminate tumour cells in vitro by direct phagocytosis. (C) 2000 Cancer Research Campaign.