Antitumor Immune Effector Mechanisms Recruited by Phage Display-derived Fully Human IgG1 and IgA1 Monoclonal Antibodies
作者： I. A. F. M. Heijnen , T. Logtenberg , E. Boel , G. Huls , E. Cuomo
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摘要: We have constructed a recombinant, fully human IgA1 monoclonal antibody, UBS-54/IgA1, against the tumor-associated Ep-CAM molecule and compared its tumor-killing capacity with IgG1 counterpart in vitro assays. The data show that phage display-derived antibodies efficiently recruit immune effector cells express Fc receptor for IgA, FcαRI (CD89). UBS-54/IgA1-mediated killing of tumor by isolated polymorphonuclear (PMNs) whole blood was found to proceed without necessity preactivate cytokines. In addition, anti-Ep-CAM antibody (huMab) triggered phagocytosis monocyte-derived macrophages. Strikingly, simultaneous addition did not result enhancement cell unless were stimulated granulocyte colony-stimulating factor. lack an additive effect could be attributed inhibitory IgG on IgA-mediated through binding FcγRIIb expressed PMNs. These results antitumor huMabs are capable recruiting large population peripheral PMNs killing. This is effectively recruited type antibodies, currently most frequently used clinical application. suggest combination may collaborate patients treated
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