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Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice.
- Source :
-
Nature medicine [Nat Med] 2014 Jun; Vol. 20 (6), pp. 676-81. Date of Electronic Publication: 2014 May 25. - Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- Animals
Immunoprecipitation
Mice
Myeloid Cells drug effects
Peptide Library
Receptors, Cell Surface immunology
S100 Proteins metabolism
Tumor Microenvironment drug effects
Myeloid Cells immunology
Neoplasms drug therapy
Neoplasms immunology
Recombinant Fusion Proteins pharmacology
Tumor Escape physiology
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1546-170X
- Volume :
- 20
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24859530
- Full Text :
- https://doi.org/10.1038/nm.3560