Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer

Carlotta Spano, Giulia Grisendi, Giulia Golinelli, Filippo Rossignoli, Malvina Prapa, Marco Bestagno, Olivia Candini, Tiziana Petrachi, Alessandra Recchia, Francesca Miselli, Giulia Rovesti, Giulia Orsi, Antonino Maiorana, Paola Manni, Elena Veronesi, Maria Serena Piccinno, Alba Murgia, Massimo Pinelli, Edwin M Horwitz, Stefano CascinuPierfranco Conte, Massimo Dominici

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive adult cancers with an unacceptable prognosis. For this reason novel therapies accounting for PDAC peculiarities, such as the relevant stromal reaction, are urgently needed. Here adipose mesenchymal stromal/stem cells (AD-MSC) have been armed to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related apoptosis-inducing ligand (sTRAIL). This cancer gene therapy strategy was in vitro challenged demonstrating that sTRAIL was thermally stable and able to induce apoptosis in the PDAC lines BxPC-3, MIA PaCa-2 and against primary PDAC cells. sTRAIL released by AD-MSC relocated into the tumor stroma was able to significantly counteract tumor growth in vivo with a significant reduction in tumor size, in cytokeratin-7+ cells and by an anti-angiogenic effect. In parallel, histology on PDAC specimens form patients (n = 19) was performed to investigate the levels of TRAIL DR4, DR5 and OPG receptors generating promising insights on the possible clinical translation of our approach. These results indicate that adipose MSC can very efficiently vehicle a novel TRAIL variant opening unexplored opportunities for PDAC treatment.

Original languageEnglish
Article number1788
Pages (from-to)1-14
Number of pages14
JournalSci. Rep.
Volume9
Issue number1
DOIs
Publication statusPublished - Feb 11 2019

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