Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice.
Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice.
复制标题
产生一种新的治疗肽，该肽会耗尽肿瘤含量的小鼠中髓样衍生的抑制细胞。
作者：
癌症免疫逃避是疾病进展的一个新标志。然而，由于缺乏可用的特定细胞表面标记物，旨在了解骨髓源性抑制细胞（MDSC）在肿瘤微环境中的作用的功能研究受到限制。我们采用竞争性肽噬菌体展示平台来鉴定特异性结合 MDSC 的候选肽，并生成肽-Fc 融合蛋白（肽体）。在多种肿瘤模型中，静脉内注射肽体可完全耗尽荷瘤小鼠的血液、脾脏和瘤内 MDSC，而不影响促炎性免疫细胞类型，例如树突状细胞。对照 Gr-1 抗体主要消耗粒细胞 MDSC，而肽体则消耗粒细胞和单核细胞亚群。值得注意的是，肽体治疗与体内肿瘤生长的抑制相关，优于 Gr-1。 MDSC 膜蛋白的免疫沉淀将 S100 家族蛋白确定为候选靶点。我们的策略可能有助于识别稀有细胞亚型（包括人类 MDSC）的新诊断和治疗表面靶点。
Cancer immune evasion is an emerging hallmark of disease progression. Functional studies to understand the role of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment however, are limited by the lack of available specific cell surface markers. We adapted a competitive peptide phage display platform to identify candidate peptides binding MDSC specifically and generated peptide-Fc fusion proteins (peptibody). In multiple tumor models peptibody injection iv completely depleted blood, splenic, and intratumoral MDSC in tumor-bearing mice, without affecting proinflammatory immune cell types, such as dendritic cells. While control Gr-1 antibody depleted primarily granulocytic MDSC, peptibodies depleted both granulocytic and monocytic subsets. Remarkably, peptibody treatment was associated with inhibition of tumor growth in vivo, which was superior to Gr-1. Immunoprecipitation of MDSC membrane proteins identified S100 family proteins as candidate targets. Our strategy may be useful to identify novel diagnostic and therapeutic surface targets on rare cell subtypes, including human MDSC.
登录
查看更多内容
影响因子：
45.3
作者：
Schuster, Stephen J.;Neelapu, Sattva S.;Kwak, Larry W.
通讯作者：
Kwak, Larry W.
促炎S100蛋白调节髓样衍生的抑制细胞的积累。
DOI：
10.4049/jimmunol.181.7.4666
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Sinha P;Okoro C;Foell D;Freeze HH;Ostrand-Rosenberg S;Srikrishna G
通讯作者：
Srikrishna G
DOI：
10.1084/jem.20080132
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
通讯作者：
Gabrilovich DI
DOI：
10.1158/1541-7786.mcr-10-0394
发表时间：
2011-02
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Ichikawa M;Williams R;Wang L;Vogl T;Srikrishna G
通讯作者：
Srikrishna G
影响因子：
6.4
作者：
Zhao, Fei;Hoechst, Bastian;Korangy, Firouzeh
通讯作者：
Korangy, Firouzeh