Regulatory activity of azabisphosphonate-capped dendrimers on human CD4 + T cell proliferation enhances ex-vivo expansio
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Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy Damien Portevin*1, Mary Poupot1, Olivier Rolland2, Cédric-Olivier Turrin2, Jean-Jacques Fournié1, Jean-Pierre Majoral2, Anne-Marie Caminade2 and Remy Poupot*1 Address: 1INSERM, U.563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, F-31300; Université Paul-Sabatier, Toulouse, F-31400, France and 2CNRS; LCC (Laboratoire de Chimie de Coordination); 205, route de Narbonne; F-31077 Toulouse, France. Université de Toulouse, UPS, INPT; LCC; F-31077 Toulouse, France Email: Damien Portevin* - [email protected]; Mary Poupot - [email protected]; Olivier Rolland - [email protected]; CédricOlivier Turrin - [email protected]; Jean-Jacques Fournié - [email protected]; Jean-Pierre Majoral - [email protected]; AnneMarie Caminade - [email protected]; Remy Poupot* - [email protected] * Corresponding authors
Published: 24 September 2009 Journal of Translational Medicine 2009, 7:82
doi:10.1186/1479-5876-7-82
Received: 27 May 2009 Accepted: 24 September 2009
This article is available from: http://www.translational-medicine.com/content/7/1/82 © 2009 Portevin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Adoptive cell therapy with allogenic NK cells constitutes a promising approach for the treatment of certain malignancies. Such strategies are currently limited by the requirement of an efficient protocol for NK cell expansion. We have developed a method using synthetic nanosized phosphonate-capped dendrimers allowing such expansion. We are showing here that this is due to a specific inhibitory activity towards CD4+ T cell which could lead to further medical applications of this dendrimer. Methods: Mononuclear cells from human peripheral blood were used to investigate the immunomodulatory effects of nanosized phosphonate-capped dendrimers on interleukin-2 driven CD4+T cell expansion. Proliferation status was investigated using flow cytometry analysis of CFSE dilution and PI incorporation experiments. Magnetic bead cell sorting was used to address activity towards individual or mixed cell sub-populations. We performed equilibrium binding assay to assess the interaction of fluorescent dendrimers with pure CD4+ T cells. Results: Phosphonate-capped dendrimers are inhibiting the activation, and therefore the proliferation; of CD4+ T cells in IL-2 stimulated PBMCs, without affecting their viability. This allows a rapid enrichment of NK cells and further expansion. We found that dendrimer acts directly on T cells, as their regulatory property is maintained when stimulating purified CD4+ T cells with anti-CD3/CD
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