Retargeting of T-cell-receptor gamma/delta+ lymphocytes against tumor cells by bispecific monoclonal antibodies. Induction of cytolytic activity and lymphokine production.

We have recently selected MAbs specific for different molecular forms of the TCR gamma/delta (expressed by distinct cell subsets), able to activate TCR gamma/delta+ cells. Two of these reagents (G1 and A13) were used for the construction of bispecific MAbs in conjunction with a MAb (Mov19) directed to ovarian carcinoma cells, using the hybrid hybridoma technique. The G1-derived bispecific MAb GM33.9 efficiently induced lysis of Mov19+ ovarian carcinoma cell lines (IGROVI and SW626) by G1+ clones in a 4-hr 51Cr-release assay. On the other hand, it was ineffective when Mov19- target cells were used. Comparable results were obtained with the A13-derived AM18.4 bispecific MAb when A13+ clones were used as effector cells. Bispecific MAbs were also able to induce secretion of IL-2 and TNF-alpha by TCR gamma/delta+ clones when Mov19+ target cells were present.