| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Fontaine, Josette Bialecki, Emilie Frisch, Benoit Ghinnagow, Reem Faveeuw, Christelle Cruz, Luis Javier Trottein, François Macho-Fernandez, Elodie |
| Description |
Author Affiliation: Macho-Fernandez E ( Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France); Cruz LJ ( Department of Endocrinology, Leiden University Medical Center, 2333 Leiden, The Netherlands); Ghinnagow R ( Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France); Fontaine J ( Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France); Bialecki E ( Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France); Frisch B ( Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7199, Université de Strasbourg, F-67401 Illkirch Cedex, France.); Trottein F ( Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France); Faveeuw C ( Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France) |
| Abstract |
Immunotherapy aiming at enhancing innate and acquired host immunity is a promising approach for cancer treatment. The invariant NKT (iNKT) cell ligand -galactosylceramide ( -GalCer) holds great promise in cancer therapy, although several concerns limit its use in clinics, including the uncontrolled response it promotes when delivered in a nonvectorized form. Therefore, development of delivery systems to in vivo target immune cells might be a valuable option to optimize iNKT cell-based antitumor responses. Using dendritic cell (DC)-depleted mice, DC transfer experiments, and in vivo active cell targeting, we show that presentation of -GalCer by DCs not only triggers optimal primary iNKT cell stimulation, but also maintains secondary iNKT cell activation after challenge. Furthermore, targeted delivery of -GalCer to CD8 (+) DCs, by means of anti-DEC205 decorated nanoparticles, enhances iNKT cell-based transactivation of NK cells, DCs, and γδ T cells. We report that codelivery of -GalCer and protein Ag to CD8 (+) DCs triggers optimal Ag-specific Ab and cytotoxic CD8(+) T cell responses. Finally, we show that targeting nanoparticles containing -GalCer and Ag to CD8 (+) DCs promotes potent antitumor responses, both in prophylactic and in therapeutic settings. Our data may have important implications in tumor immunotherapy and vaccine development. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
2 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antigens, Cd8 Immunology Dendritic Cells Galactosylceramides Natural Killer T-cells Neoplasms, Experimental Animals Antibodies Chemistry Antigen Presentation Antigens, Cd Metabolism Cd8-positive T-lymphocytes Cell Line, Tumor Drug Delivery Systems Administration & Dosage Lectins, C-type Lymphocyte Activation Mice Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Minor Histocompatibility Antigens Nanoparticles Pathology Therapy Receptors, Antigen, T-cell, Gamma-delta Receptors, Cell Surface T-lymphocytes T-lymphocytes, Cytotoxic Tumor Burden Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
