title: Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice.
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.
authors.affiliation: 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].
authors.forename: Hong
authors.initials: H
authors.lastname: Qin
authors.affiliation: 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].
authors.forename: Beatrisa
authors.initials: B
authors.lastname: Lerman
authors.affiliation: 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].
authors.forename: Ippei
authors.initials: I
authors.lastname: Sakamaki
authors.affiliation: 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.
authors.forename: Guowei
authors.initials: G
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Soungchul C
authors.initials: SC
authors.lastname: Cha
authors.affiliation: 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.
authors.forename: Sheetal S
authors.initials: SS
authors.lastname: Rao
authors.affiliation: 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.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Qian
authors.affiliation: 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.
authors.forename: Yared
authors.initials: Y
authors.lastname: Hailemichael
authors.affiliation: 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.
authors.forename: Roza
authors.initials: R
authors.lastname: Nurieva
authors.affiliation: 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.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Dwyer
authors.affiliation: Institute of Immunology, University of Muenster, Muenster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
authors.affiliation: 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.
authors.forename: Willem W
authors.initials: WW
authors.lastname: Overwijk
authors.affiliation: 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.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
mesh_terms: D000818:Animals; D047468:Immunoprecipitation; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D019151:Peptide Library; D011956:Receptors, Cell Surface / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D009418:S100 Proteins / Q000378:metabolism; D019139:Tumor Escape / Q000502:physiology*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology*
chemical_list: D019151:Peptide Library; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D009418:S100 Proteins; C551746:granulocyte receptor 1, mouse