Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice

Using an adapted competitive peptide phage display platform, Hong Qin and colleagues identify new candidate peptides specifically binding myeloid-derived suppressor cells (MDSCs), with which they generate peptide-Fc fusion proteins (peptibodies). The peptibodies deplete intra-umoral MDSCs in several...

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Bibliographic Details
Published in:	Nature medicine Vol. 20; no. 6; pp. 676 - 681
Main Authors:	Qin, Hong, Lerman, Beatrisa, Sakamaki, Ippei, Wei, Guowei, Cha, Soungchul C, Rao, Sheetal S, Qian, Jianfei, Hailemichael, Yared, Nurieva, Roza, Dwyer, Karen C, Roth, Johannes, Yi, Qing, Overwijk, Willem W, Kwak, Larry W
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-06-2014 Nature Publishing Group
Subjects:	13/31 38/109 631/1647/664/2228 64/60 82/1 82/80 82/81 82/83 Analysis Animals Biomedicine Blood Cancer Research Care and treatment Development and progression Genetic aspects Health aspects Immune response Immunoglobulins Immunoprecipitation Immunotherapy Infectious Diseases Injection Metabolic Diseases Mice Molecular Medicine Myeloid Cells - drug effects Myeloid Cells - immunology Neoplasms - drug therapy Neoplasms - immunology Neurosciences Peptide Library Peptides Physiological aspects Proteins Receptors, Cell Surface - immunology Recombinant Fusion Proteins - pharmacology S100 Proteins - metabolism technical-report Tumor Escape - physiology Tumor Microenvironment - drug effects Tumor Microenvironment - immunology Tumors United States
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Summary:	Using an adapted competitive peptide phage display platform, Hong Qin and colleagues identify new candidate peptides specifically binding myeloid-derived suppressor cells (MDSCs), with which they generate peptide-Fc fusion proteins (peptibodies). The peptibodies deplete intra-umoral MDSCs in several mouse tumor models, in addition to those in blood and spleen, with limited off-target activity and superiority over standard depletion methods. Validation of this approach for cell type–specific surface marker discovery identified S100A9 as a target on the surface of MDSCs. Immune evasion is an emerging hallmark of cancer progression. However, functional studies to understand the role of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are limited by the lack of available specific cell surface markers. We adapted a competitive peptide phage display platform to identify candidate peptides binding MDSCs specifically and generated peptide-Fc fusion proteins (peptibodies). In multiple tumor models, intravenous peptibody injection completely depleted blood, splenic and intratumoral MDSCs in tumor-bearing mice without affecting proinflammatory immune cell types, such as dendritic cells. Whereas control Gr-1–specific antibody primarily depleted granulocytic MDSCs, peptibodies depleted both granulocytic and monocytic MDSC subsets. Peptibody treatment was associated with inhibition of tumor growth in vivo , which was superior to that achieved with Gr-1–specific antibody. Immunoprecipitation of MDSC membrane proteins identified S100 family proteins as candidate targets. Our strategy may be useful to identify new diagnostic and therapeutic surface targets on rare cell subtypes, including human MDSCs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-8956 1546-170X
DOI:	10.1038/nm.3560