Tumor therapy with bispecific antibody: The targeting and triggering stepscan be separated employing a CD2-based strategy

For tumor therapy with unprimed effector cells, we developed a novel combin ation of a CD2 x tumor Ag bispecific targeting Ab and an anti-CD2 triggerin g Ab, These Ab constructs were derived from two novel CD2 mAbs, termed M1 a nd M2 that, together, but not individually activate T cells. Unlike many ot her CD2 Abs, M1 and M2 do not interfere with TCR/CD3 triggering nor do they inhibit binding of CD2 to its ligand CD58, thus preserving the physiologic al functions of these important effector cell molecules, M2 was chemically conjugated with an Ab recognizing the epidermal growth factor-receptor (EGF -R). Incubation of unprimed peripheral blood mononuclear cells with the bis pecific F(ab')(2) construct (M2xEGF-R) in the presence of trigger Ab M1 led to efficient selective lysis of EGF-R-positive targets by CTL and NK cells . Importantly, the need for trigger rib M1 for effector cell stimulation al lowed to separate targeting from triggering steps in vitro and should thus enable to focus immune responses to sites of target Ag expression in vivo.