Details

Autor(en) / Beteiligte

• Buscail, Louis
• Bournet, Barbara
• Vernejoul, Fabienne
• Cambois, Gilles
• Lulka, Hubert
• Hanoun, Naima
• Meulle, Aline
• Vignolle-Vidoni, Alix
• Barbey, Odile
• Gross, Fabian
• Guimbaud, Rosine
• Ottal, Philippe
• Tiraby, Gérard
• Cordelier, Pierre

Titel

Abstract B96: Non-viral gene therapy for pancreatic cancer, from preclinical models to phase II clinical trial

Ist Teil von

• Cancer research (Chicago, Ill.), 2015-07, Vol.75 (13_Supplement), p.B96-B96

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract To date, pancreatic adenocarcinoma (PDAC) can’t be diagnosed early. Consequently, a majority of patient (80%) display an advanced disease that results in a low resection rate leading to a dismal overall median survival of less than 6 months. We extensively demonstrated that delivering SSTR2, DCK and UMK genes using non-viral vectors strongly inhibit tumor progression and dissemination in relevant experimental models of PDAC. Consequently, we designed a GMP-grade gene therapy product, namely CYL-02, encoding for the above mentioned therapeutic proteins, delivered by a non-viral vector for the management of 24 patients diagnosed with advanced PDAC. In this phase I clinical trial, gene therapy was administered in dose-escalation in the tumors using endoscopic ultrasound. Patients received gemcitabine during this protocol. We demonstrate that the intratumoral injection of the gene therapy product is feasible, well tolerated and safe, and results in the presence and the expression of CYL-02 in the tumors. Consequently, tumor progression is inhibited during the course of the protocol. In patients with locally advanced PDAC at the time of diagnosis, tumor size and serum levels of CA 19-9 significantly decreased following gene therapy regardless of the previous lines of treatment and median progression free survival and median overall survival reaches 6.4 and 11.4 months respectively. In addition, we carried out several advanced proteomic and circulating miRNAs analyses to identify diagnostic biomarkers predictive and/or indicative of treatment response and follow-up, to select clinical trial participants and/or to tailor therapy for individual patient. We already identified several biomarkers of clinical interest using either CE-MS (capillary electrophoresis coupled with mass spectrometry) or high throughput q(RT)PCR for peptide and miRNA identification, respectively, to create a clear prescription path for gene therapy in forthcoming clinical trials. Based on these preliminary yet very encouraging results, we propose that patients may clinically benefit from this approach. Accordingly, we are now entering phase II clinical trial using CYL-02 gene therapy product in patients diagnosed with locally advanced PDAC. Citation Format: Louis Buscail, Barbara Bournet, Fabienne Vernejoul, Gilles Cambois, Hubert Lulka, Naima Hanoun, Aline Meulle, Alix Vignolle-Vidoni, Odile Barbey, Fabian Gross, Rosine Guimbaud, Philippe Ottal, Gérard Tiraby, Pierre Cordelier. Non-viral gene therapy for pancreatic cancer, from preclinical models to phase II clinical trial. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B96.