Details

Autor(en) / Beteiligte

• Park, Jason
• Wrzesinski, Stephen H
• Stern, Eric
• Look, Michael
• Criscione, Jason
• Ragheb, Ragy
• Jay, Steven M
• Demento, Stacey L
• Agawu, Atu
• Licona Limon, Paula
• Ferrandino, Anthony F
• Gonzalez, David
• Habermann, Ann
• Flavell, Richard A
• Fahmy, Tarek M

Titel

Combination delivery of TGF-[beta] inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy

Ist Teil von

• Nature materials, 2012-10, Vol.11 (10), p.895

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The tumour microenvironment thwarts conventional immunotherapy through multiple immunologic mechanisms, such as the secretion of the transforming growth factor-β (TGF-β), which stunts local tumour immune responses. Therefore, high doses of interleukin-2 (IL-2), a conventional cytokine for metastatic melanoma, induces only limited responses. To overcome the immunoinhibitory nature of the tumour microenvironment, we developed nanoscale liposomal polymeric gels (nanolipogels; nLGs) of drug-complexed cyclodextrins and cytokine-encapsulating biodegradable polymers that can deliver small hydrophobic molecular inhibitors and water-soluble protein cytokines in a sustained fashion to the tumour microenvironment. nLGs releasing TGF-β inhibitor and IL-2 significantly delayed tumour growth, increased survival of tumour-bearing mice, and increased the activity of natural killer cells and of intratumoral-activated CD8(+) T-cell infiltration. We demonstrate that the efficacy of nLGs in tumour immunotherapy results from a crucial mechanism involving activation of both innate and adaptive immune responses. [PUBLICATION ABSTRACT]