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Highly Efficient Elimination of Colorectal Tumor- Initiating Cells by an EpCAM/CD3-Bispecific Antibody

By Engaging Human, T Cells, Ines Herrmann, Patrick A. Baeuerle, Matthias Friedrich, Er Murr, Susanne Filusch, Dominik Rüttinger, Mariam W. Majdoub, Sherven Sharma, Peter Kufer and Tobias Raum

Abstract

With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs) are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof

Year: 2010
OAI identifier: oai:CiteSeerX.psu:10.1.1.352.266
Provided by: CiteSeerX
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