Is antibody therapy of tumor compromised promised by infusion-related reactions? A case for inhibiting the activity of cyclooxygenase-2

Evidence suggests that amelioration of childhood immune thrombocytopenic purpura and some other autoimmune states by intravenous normal IgG is due to the following chain of events: (1) cross-linking of Fcgamma-receptors on blood effector cells; (2) release of mediators from these cells, often yielding an infusion-related reaction; (3) mediator-induced development of a cytokine field characterized by a mutually stabilizing Th2 polarization of CD4 T lymphocytes and alternative activation of macrophages; (4) selective quiescence of these macrophages towards targets coated with IgG autoantibody, due to increased expression of the macrophage Fcgamma-receptor IIB. In this paper it is postulated that in the field of antibody therapy of tumor, an undesirable delayed or absent subsidence of antibody-coated tumor is due to immunomodulation of the same type as yields amelioration of autoimmunity, and arising from a similar chain of events. If the postulate is correct the chain could usefully be broken at the level of mediator action, possibly by blocking that increased synthesis of prostaglandin E-2 which is catalyzed by the enzyme cyclooxygenase-2. (C) 2004 Elsevier Ltd. All rights reserved.