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

Arnon, Tal I. and Markel, Gal and Bar-Ilan, Ahuva and Hanna, Jacob and Fima, Eyal and Benchetrit, Fabrice and Galili, Ruth and Cerwenka, Adelheid and Benharroch, Daniel and Sion-Vardy, Netta and Porgador, Angel and Mandelboim, Ofer (2008) Harnessing Soluble NK Cell Killer Receptors for the Generation of Novel Cancer Immune Therapy. PLoS ONE, 3 (5). Art. No. e2150. ISSN 1932-6203. PMCID PMC2364651; PMC4418968. https://resolver.caltech.edu/CaltechAUTHORS:ARNplosone08

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pone.0002150DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364651/PubMed CentralArticle
http://dx.doi.org/10.1371/journal.pone.0128052DOICorrection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418968/PubMed CentralCorrection
Additional Information:© 2008 Arnon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: February 12, 2008; Accepted: April 1, 2008; Published: May 14, 2008. Funding: The authors have no support or funding to report. [see Formal correction]. Conceived and designed the experiments: OM TA AP. Performed the experiments: TA. Analyzed the data: OM TA AP. Contributed reagents/materials/analysis tools: TA GM AB JH EF FB RG AC DB NS AP. Wrote the paper: TA. Competing interests: The authors have declared that no competing interests exist. Formal Correction: Correction to Funding The funding information for this paper is missing. It should read: This work was supported by the Israel Science Foundation (O.M.), the Binational Science Foundation (O.M.), the AICR (O.M), the ICRF (O.M.), the European Commission (LSHC-CT-2002-518178 and MRTN-CT-2005 to O.M.), the Israel Ministry of Health (A.P.), the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ), and Israeli's Ministry of Science and Technology (MOST) (A.P.).
Funders:
Funding AgencyGrant Number
Israel Science FoundationUNSPECIFIED
Binational Science Foundation (USA-Israel)UNSPECIFIED
American Institute for Cancer ResearchUNSPECIFIED
European CommissionLSHC-CT-2002-518178
European CommissionMRTN-CT-2005
Israel Ministry of HealthUNSPECIFIED
Deutsches Krebsforschungszentrum (DKFZ)UNSPECIFIED
Ministry pf Science and Technology (MOST) (Israel)UNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC2364651; PMC4418968
Record Number:CaltechAUTHORS:ARNplosone08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:ARNplosone08
Usage Policy:© 2008 Arnon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ID Code:11846
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:06 Oct 2008 22:08
Last Modified:12 Feb 2020 21:40

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