Format

Send to

Choose Destination
Nat Med. 2014 Jun;20(6):676-81. doi: 10.1038/nm.3560. Epub 2014 May 25.

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

Author information

1
1] Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [3].
2
1] Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [3] The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA. [4].
3
1] Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
4
1] Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
5
1] Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
6
1] Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
7
Institute of Immunology, University of Muenster, Muenster, Germany.
8
1] Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [3] The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.

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.

PMID:
24859530
PMCID:
PMC4048321
DOI:
10.1038/nm.3560
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center