Cytotoxic Mechanisms of Tumor Specific Antibodies
Annual summary rept. 30 Sep 1999-29 Sep 2002
COLUMBIA UNIV NEW YORK
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Many mechanisms have been proposed to account for the anti-tumor activities of therapeutic antibodies, blockade of signaling pathways, activation of apoptosis and effector-cell- mediated cytotoxicity ADCC. However we have demonstrated Clynes RA, et al., Nature Medicine 6443-446 2000 that engagement of Fcgamma receptors on effector cells is a dominant component of the in vivo activity of antibodies against tumors. Engagement of activating Fc receptors FcRI andor III was required for the in vivo activity of mouse monoclonal antibodies and vaccines in syngenic melanoma models, as well as of humanized, clinically effective therapeutic mAbs Herceptin and Rituxan in breast cancer and lymphoma xenograft system .
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