Harnessing Soluble NK Cell Killer Receptors for the Generation of Novel Cancer Immune Therapy

被引：27

作者：

Arnon, Tal I. ^{[1
]}

Markel, Gal ^{[2
]}

Bar-Ilan, Ahuva ^{[3
]}

Hanna, Jacob ^{[4
]}

Fima, Eyal ^{[3
]}

Benchetrit, Fabrice ^{[3
]}

Galili, Ruth ^{[5
]}

Cerwenka, Adelheid ^{[6
]}

Benharroch, Daniel ^{[7
]}

Sion-Vardy, Netta ^{[7
]}

Porgador, Angel ^{[3
]}

Mandelboim, Ofer ^{[5
]}

机构：

[1] CALTECH, Div Biol, Pasadena, CA 91125 USA

[2] Sheba Med Ctr, Sheba Canc Res Ctr, Tel Hashomer, Israel

[3] Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, Shraga Segal Dept Microbiol & Immunol, Beer Sheva, Israel

[4] Whitehead Inst Biomed Res, Cambridge, MA USA

[5] Hebrew Univ Hadassah Med Sch, Lautenberg Ctr General & Tumor Immunol, Jerusalem, Israel

[6] German Canc Res Ctr, Div Innate Immun, Heidelberg, Germany

[7] Soroka Hosp, Pathol Dept, Beer Sheva, Israel

来源：

PLOS ONE | 2008年 / 3卷 / 05期

关键词：

D O I：

10.1371/journal.pone.0002150

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

The natural cytotoxic receptors (NCRs) are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. The NCRs, which include three members; NKp46, NKp44 and NKp30, are critically involved in NK cytotoxicity against different targets, including a wide range of tumor cells derived from various origins. Even though the tumor ligands of the NCRs have not been identified yet, the selective manner by which these receptors target tumor cells may provide an excellent basis for the development of novel anti-tumor therapies. To test the potential use of the NCRs as anti-tumor agents, we generated soluble NCR-Ig fusion proteins in which the constant region of human IgG1 was fused to the extracellular portion of the receptor. We demonstrate, using two different human prostate cancer cell lines, that treatment with NKp30-Ig, dramatically inhibits tumor growth in vivo. Activated macrophages were shown to mediate an ADCC response against the NKp30-Ig coated prostate cell lines. Finally, the Ig fusion proteins were also demonstrated to discriminate between benign prostate hyperplasia and prostate cancer. This may provide a novel diagnostic modality in the difficult task of differentiating between these highly common pathological conditions.

引用

页数：10

共 44 条

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