Enhanced Stimulation of Anti-Ovarian Cancer CD8+ T Cells by Dendritic Cells Loaded with Nanoparticle Encapsulated Tumor Antigen

• Published in: American journal of reproductive immunology (1989) Vol. 65; no. 6; pp. 597 - 609
• Main Authors: Hanlon, Douglas J., Aldo, Paulomi B., Devine, Lesley, Alvero, Ayesha B., Engberg, Anna K., Edelson, Richard, Mor, Gil
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2011
• Subjects: Antigen Presentation; Antigens, Differentiation - metabolism; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Carcinoma - immunology; Carcinoma - pathology; Carcinoma - therapy; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cells, Cultured; Cytokines - metabolism; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Dendritic Cells - transplantation; Female; Humans; Immunotherapy, Adoptive; Lactic Acid - chemistry; Lymphocyte Activation; nanoparticle; Nanoparticles - chemistry; Nanoparticles - therapeutic use; ovarian cancer; Ovarian Neoplasms - immunology; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Polyglycolic Acid - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer; tumor antigens; vaccine
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/j.1600-0897.2010.00968.x

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.