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Keywords:

  • CD8+ T cells;
  • dendritic cells;
  • nanoparticle;
  • ovarian cancer;
  • tumor antigens;
  • vaccine

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.