Enhancement of polymorphonuclear cell-mediated tumor cell killing on simultaneous engagement of Fc gamma RI (CD64) and Fc alpha RI (CD89)

Antibodies can efficiently induce antitumor responses via recruitment of Fc receptor-bearing cytotoxic cells. Polymorphonuclear (PMN) cells represent attractive effector cells for antibody-directed immunotherapy. This, becaus e activated PMN cells coexpress the class I receptors for IgG (Fc gamma RI, CD64) and IgA (Fc alpha RI, CD89), which are potent cytotoxic trigger mole cules. Both receptors, however, require the FcR gamma chain for signaling. In this study, we show that Fc gamma RI and Fc alpha RI can trigger functio n independently of one another and do not cross-compete for the FcR gamma c hain. Fc alpha RI proved more efficient in initiating early signaling event s and effector functions, such as redirected tumor cell killing and generat ion of superoxide. In addition, simultaneous engagement of Fc gamma RI and Fc alpha RI resulted in enhanced tumor cell lysis. These data support the d evelopment of concepts in which both Fc gamma RI and Fc alpha RI on PMN cel ls are targeted for tumor therapy.