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Antibody-Fc receptor (FcR) interactions play an important role in the mechanism of action of most therapeutic antibodies against cancer. Effector cell activation through FcR triggering may induce tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC). Reciprocally, FcR cross-linking of antibody may lead to the induction of apoptotic signaling in tumor cells. The relative importance of these bisecting pathways to in vivo antibody activity is unknown. To unravel these roles, we developed a novel mouse model with normal FcR expression but in which FcR signaling was inactivated by mutation of the associated γ-chain. Transgenic mice showed similar immune complex binding compared with wild-type mice. In contrast, ADCC of cells expressing frequently used cancer targets, such as CD20, epidermal growth factor receptor, Her2, and gp75, was abrogated. Using the therapeutic CD20 antibodies ofatumumab and rituximab, we show that FcR cross-linking of antibody-antigen immune complexes in the absence of γ-chain signaling is insufficient for their therapeutic activity in vivo. ADCC therefore represents an essential mechanism of action for immunotherapy of lymphoid tumors. Cancer Res; 70(8); 3209-17. ©2010 AACR.

No abstract

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. Ecological Society of America is collaborating with JSTOR to digitize, preserve and extend access to Ecology.Abstract. Brown hares (Lepus europaeus) are shown to facilitate grazing by Brent Geese (Branta bernicla) in a temperate salt marsh in the Netherlands by retarding vegetation succession for >25 yr. Winter grazing by hares prevented the shrub Atriplex portulacoides from spreading in younger parts of the salt marsh. Clipping experiments showed that Atriplex had poor recovery after removal of aboveground tissue, which makes Atriplex vulnerable for hare attack. Once Atriplex swards were cut to the ground to mimic hare grazing, Brent Geese visited those sites more than twice as frequently than untouched control plots. Goose visitation was reduced when bushes of Atriplex were planted. Large parts of the core feeding area of Brent Geese would be unsuitable for goose grazing if hares were not present. A reduction of at least 44% in the carrying capacity of the marsh for Brent Geese was calculated in the absence of hares. Vulnerability of Atriplex to hare grazing and the high food intake of geese are key elements to this facilitative pattern. Additionally, hares reduced the number of dead Artemisia maritima stems in grassy swards, which otherwise might have hampered grazing by geese. Facilitation by herbivores such as hare, rabbit, cattle, and sheep is likely to be a prominent factor enhancing feeding conditions for Brent Geese all along the northwest European coast.