Inhibition of tumor metastasis: functional immune modulation of the CUB domain containing protein 1.

Molecular Pharmaceutics
Keisuke FukuchiKim D Janda

Abstract

Despite significant progress and notable successes in tumor therapy, malignant disease remains an extremely difficult problem in today's health care setting. There is, however, an increasing application of new therapies targeting proteins specifically upregulated on tumor cells. These innovative therapeutic approaches are aimed at molecules that contribute to malignant development and progression but spare normal tissues. The CUB domain containing protein 1 (CDCP1) is such a tumor-associated protein and, thus, a potential candidate for targeted cancer immunotherapy. Herein, we describe the generation of function-blocking human antibodies against CDCP1 that were obtained from human scFv phage display libraries using subtractive panning protocols on CDCP1 expressing cancer cells and immunopurified CDCP1 protein. One of the isolated anti-CDCP1 antibodies, namely, C20Fc, efficiently blocked experimental metastasis of human carcinoma cells, including HeLa cells stably transfected with CDCP1 and prostate carcinoma cells PC-hi/diss naturally expressing CDCP1, in both chick embryo and mouse model systems. The C20Fc antibody also reduced colony formation of CDCP1 expressing cells in a soft agar assay for anchorage-independent cell growt...Continue Reading

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Citations

Jun 27, 2012·The Journal of Experimental Medicine·Antonio DiGiandomenicoC Kendall Stover
Aug 5, 2011·Cancer Science·Takamasa Uekita, Ryuichi Sakai
Feb 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Brooke M EmerlingLewis C Cantley
Mar 8, 2018·Oncogene·Sara G PollanBeatrice S Knudsen

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