USE OF ANTI-CD3 AND ANTI-CD16 BISPECIFIC MONOCLONAL-ANTIBODIES FOR THE TARGETING OF T-CELLS AND NK CELLS AGAINST TUMOR-CELLS

To target T lymphocytes against EGF-R+ tumors, we constructed anti-CD3 /anti-EGF-R bimAbs either by the generation of a hybrid hybridoma (qua droma) or by a chemical cross-linking method. Analysis of the in vitro functional activity of these two different constructs indicated that the quadroma-secreted bimAb was more efficient in targeting the CD3+8 clones against EGF-R+ target cells with respect to the bimAb produced by chemical method. In addition, the quadroma-produced bimAb is able to induce cytolysis of EGF-R+ tumor cell lines of PHA-induced lymphobl asts that had been expanded in IL-2-containing medium, whereas tumor c ells lacking expression of EGF-R were not lysed. Resting PBL targeted by the bimAb did not display significant cytotoxicity against the rele vant tumor. An anti-CD16 hybridoma (IgG1) was fused with an anti-folat e-binding protein hybrid (IgG2a) to construct bimAbs to target NK cell s against NK-resistant ovarian carcinomas. The hybrid IgG1/IgG2a bimAb triggered the specific lysis of relevant target cells by resting NK c ells, but it was ineffective when CD8+TCRalpha/beta+ cultured cell pop ulations were used as effectors. Only marginal increases of cytolytic activity could be induced by the bimAb when IL-2-activated PBL (i.e., LAK cells) were used as effectors due to the high cytolytic activity o f these cells against the relevant tumors in the absence of bimAb. The possible use of anti-CD16 or anti-CD3 bimAbs for the development of d ifferent cellular immunotherapy strategies against cancer is discussed .