Superior In vivo Efficacy of Afucosylated Trastuzumab in the Treatment of HER2-Amplified Breast Cancer
TT Junttila, K Parsons, C Olsson, Y Lu, Y Xin… - Cancer research, 2010 - AACR
TT Junttila, K Parsons, C Olsson, Y Lu, Y Xin, J Theriault, L Crocker, O Pabonan, T Baginski…
Cancer research, 2010•AACRThe enhancement of immune effector functions has been proposed as a potential strategy
for increasing the efficacy of therapeutic antibodies. Here, we show that removing fucose
from trastuzumab (Herceptin) increased its binding to FcγRIIIa, enhanced antibody-
dependent cell-mediated cytotoxicity, and more than doubled the median progression-free
survival when compared with conventional trastuzumab in treating preclinical models of
HER2-amplified breast cancer. Our results show that afucosylated trastuzumab has superior …
for increasing the efficacy of therapeutic antibodies. Here, we show that removing fucose
from trastuzumab (Herceptin) increased its binding to FcγRIIIa, enhanced antibody-
dependent cell-mediated cytotoxicity, and more than doubled the median progression-free
survival when compared with conventional trastuzumab in treating preclinical models of
HER2-amplified breast cancer. Our results show that afucosylated trastuzumab has superior …
Abstract
The enhancement of immune effector functions has been proposed as a potential strategy for increasing the efficacy of therapeutic antibodies. Here, we show that removing fucose from trastuzumab (Herceptin) increased its binding to FcγRIIIa, enhanced antibody-dependent cell-mediated cytotoxicity, and more than doubled the median progression-free survival when compared with conventional trastuzumab in treating preclinical models of HER2-amplified breast cancer. Our results show that afucosylated trastuzumab has superior efficacy in treating in vivo models of HER2-amplified breast cancer and support the development of effector function–enhanced antibodies for solid tumor therapy. Cancer Res; 70(11); 4481–9. ©2010 AACR.
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