Enhanced Stimulation of Anti-Ovarian Cancer CD8+ T Cells by Dendritic Cells Loaded with Nanoparticle Encapsulated Tumor Antigen
Article first published online: 18 JAN 2011
© 2011 John Wiley & Sons A/S
American Journal of Reproductive Immunology
Volume 65, Issue 6, pages 597–609, June 2011
How to Cite
Hanlon, D. J., Aldo, P. B., Devine, L., Alvero, A. B., Engberg, A. K., Edelson, R. and Mor, G. (2011), Enhanced Stimulation of Anti-Ovarian Cancer CD8+ T Cells by Dendritic Cells Loaded with Nanoparticle Encapsulated Tumor Antigen. American Journal of Reproductive Immunology, 65: 597–609. doi: 10.1111/j.1600-0897.2010.00968.x
- Issue published online: 25 APR 2011
- Article first published online: 18 JAN 2011
- Submitted December 6, 2010; accepted December 9, 2010.
- CD8+ T cells;
- dendritic cells;
- ovarian cancer;
- tumor antigens;
Citation Hanlon DJ, Aldo PB, Devine L, Alvero AB, Engberg AK, Edelson R, Mor G. Enhanced stimulation of anti-ovarian cancer CD8+ T cells by dendritic cells loaded with nanoparticle encapsulated tumor antigen. Am J Reprod Immunol 2011; 65: 597–609
Problem Dendritic cell (DC)-based cancer therapies are favored approaches to stimulate anti-tumor T-cell responses. Unfortunately, tolerance to tumor antigens is difficult to overcome. Biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) are effective reagents in the delivery of drugs and tumor-associated antigens (TAA). In this study, we assessed the capacity of a PLGA NP-based delivery system to augment CD8 T-cell responses to ovarian cancer TAA.
Method of Study Human DC were generated from blood monocytes by conventional in vitro differentiation and loaded with either soluble tumor lysate or NP/lysate conjugates (NPL). These antigen-loaded DC were then used to stimulate autologous CD8+ T cells. Cytokine production and activation markers were evaluated in the CD8+ T cells.
Results DC loading with NPL increased cytokine production by stimulated CD8 T cells and induced T-cell expression of cell surface co-stimulatory molecules, typical of anti-tumor immune responses. In contrast, delivery of naked tumor lysate antigens preferentially induced a T-cell profile characteristic of tolerization/exhaustion.
Conclusion These findings indicate that delivery of TAA in NP enables DC to efficiently activate anti-tumor CD8+ T cells. PLGA NP encapsulation of tumor-derived lysate protein antigens is an encouraging new preparative methodology for DC-based vaccination meriting clinical testing.