Pre-clinical characterization of GMP grade CCL21-gene modified dendritic cells for application in a phase I trial in Non
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Pre-clinical characterization of GMP grade CCL21-gene modified dendritic cells for application in a phase I trial in Non-Small Cell Lung Cancer Felicita Baratelli†1, Hiroko Takedatsu†1, Saswati Hazra1, Katherine Peebles1, Jie Luo1, Pam S Kurimoto1, Gang Zeng4, Raj K Batra1,3, Sherven Sharma1,3, Steven M Dubinett1,2,3 and Jay M Lee*1,5 Address: 1UCLA Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Los Angeles, CA 90095, USA, 2Department of Pathology and Laboratory Medicine, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA, 3Molecular Medicine Laboratory, Veteran's Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA, 4Department of Urology, Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA and 5Division of Cardiothoracic Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA Email: Felicita Baratelli - [email protected]; Hiroko Takedatsu - [email protected]; Saswati Hazra - [email protected]; Katherine Peebles - [email protected]; Jie Luo - [email protected]; Pam S Kurimoto - [email protected]; Gang Zeng - [email protected]; Raj K Batra - [email protected]; Sherven Sharma - [email protected]; Steven M Dubinett - [email protected]; Jay M Lee* - [email protected] * Corresponding author †Equal contributors
Published: 22 July 2008 Journal of Translational Medicine 2008, 6:38
doi:10.1186/1479-5876-6-38
Received: 5 February 2008 Accepted: 22 July 2008
This article is available from: http://www.translational-medicine.com/content/6/1/38 © 2008 Baratelli 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: Our previous studies have demonstrated that transduction of human dendritic cells (DC) with adenovirus encoding secondary lymphoid chemokine, CCL21, led to secretion of biologically active CCL21 without altering DC phenotype or viability. In addition, intratumoral injections of CCL21-transduced DC into established murine lung tumors resulted in complete regression and protective anti-tumor immunity. These results have provided the rationale to generate a clinical grade adenoviral vector encoding CCL-21 for ex vivo transduction of human DC in order to assess intratumoral administration in late stage human lung cancer. Methods: In the current study, human monocyte-derived DC were differentiated by exposure to GM-CSF and IL-4 from cryopreserved mononuclear cells obtained from healthy volunteers. Transduction with clinical grade adenoviral vector encoding CCL21 (1167 viral particles per cell) resulted in secretion of CCL21 protein. Results: CCL21 protein pr
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