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 (IGROV1 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.