Co-delivery of PLGA encapsulated invariant NKT cell agonist with antigenic protein induce strong T cell-mediated antitumor immune responses
| Autor: | Eric A. W. van Dinther, Martin Kreutz, Jurjen Tel, Uzi Gileadi, Vincenzo Cerundolo, Yusuf Dolen, Angela Vasaturo, Carl G. Figdor, Maaike A. van Hout-Kuijer |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment T cell Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Immunology Cell chemical and pharmacologic phenomena 03 medical and health sciences Immune system Antigen medicine melanoma Immunology and Allergy Cytotoxic T cell Original Research CTL response biology Chemistry nanoparticle PLGA 3. Good health Cell biology Ovalbumin 030104 developmental biology medicine.anatomical_structure α-GalCer Oncology biology.protein Adjuvant CD8 |
| Zdroj: | Oncoimmunology, 5, 1, pp. e1068493 Oncoimmunology, 5, e1068493 Oncoimmunology |
| ISSN: | 2162-4011 |
| Popis: | Contains fulltext : 172141.pdf (Publisher’s version ) (Open Access) Antitumor immunity can be enhanced by the coordinated release and delivery of antigens and immune-stimulating agents to antigen-presenting cells via biodegradable vaccine carriers. So far, encapsulation of TLR ligands and tumor-associated antigens augmented cytotoxic T cell (CTLs) responses. Here, we compared the efficacy of the invariant NKT (iNKT) cell agonist alpha-galactosylceramide (alpha-GalCer) and TLR ligands (R848 and poly I:C) as an adjuvant for the full length ovalbumin (OVA) in PLGA nanoparticles. We observed that OVA+alpha-GalCer nanoparticles (NP) are superior over OVA+TLR-L NP in generating and stimulating antigen-specific cytotoxic T lymphocytes without the need for CD4+ T cell help. Not only a 4-fold higher induction of antigen-specific T cells was observed, but also a more profound IFN-gamma secretion was obtained by the addition alpha-GalCer. Surprisingly, we observed that mixtures of OVA containing NP with alpha-GalCer were ineffective, demonstrating that co-encapsulation of both alpha-GalCer and antigen within the same nanoparticle is essential for the observed T cell responses. Moreover, a single immunization with OVA+alpha-GalCer NP provided substantial protection from tumor formation and even delayed the growth of already established tumors, which coincided with a prominent and enhanced antigen-specific CD8+ T cell infiltration. The provided evidence on the advantage of antigen and alpha-GalCer coencapsulation should be considered in the design of future nanoparticle vaccines for therapeutic purposes. |
| Databáze: | OpenAIRE |
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