Journal article
Antibodies targeted to TRAIL receptor-2 and ErbB-2 synergize in vivo and induce an antitumor immune response
J Stagg, J Sharkey, S Pommey, R Young, K Takeda, H Yagita, RW Johnstone, MJ Smyth
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2008
Abstract
Despite the development of human epidermal growth factor receptor-2 (ErbB-2/HER2)-targeted therapies, there remains an unmet medical need for breast cancer patients with ErbB-2 overexpression. We investigated the therapeutic activity of an agonist mAb to mouse tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 (DR5) against ErbB2-driven breast cancer. Established tumors in BALB/c transgenic mice expressing a constitutively active ErbB-2/neuT were treated with anti-DR5 mAb and/or anti-ErbB-2 mAb and monitored for tumor progression. Treatment with anti-DR5 or anti-ErbB2 mAb as single agents significantly delayed tumor growth, although all tumors eventually progressed. R..
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Funding Acknowledgements
This work was supported by a Susan G. Komen for the Cure Grant. J. Stagg is supported by a Canadian Institutes of Health Research Fellowship. R.W.J. is a Pfizer Australia Research Fellow and is supported by a National Health and Medical Research Council of Australia Program Grant, the Cancer Council Victoria, and the Leukemia Foundation of Australia. M.J.S. is supported by a National Health and Medical Research Council Australia Research Fellowship and Program Grant.