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 (Gl and A13) were used for the construction of bispecific MAbs in conjunction with a MAb (Mov 19) directed to ovarian carcinoma cells, using the hybrid hybridoma technique. The Gl‐derived bispecific MAb GM33.9 efficiently induced lysis of Mov19 ovarian carcinoma cell lines (IGROV1 and SW626) by Gl⁺ 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.