Toll-like receptor 3-induced immune response by poly(d,l-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy

Int J Nanomedicine. 2016 Nov 2:11:5729-5742. doi: 10.2147/IJN.S109001. eCollection 2016.

Abstract

Dendritic cells (DCs) are potent professional antigen-presenting cells that are capable of initiating a primary immune response and activating T cells, and they play a pivotal role in the immune responses of the host to cancer. Prior to antigen presentation, efficient antigen and adjuvant uptake by DCs is necessary to induce their maturation and cytokine generation. Nanoparticles (NPs) are capable of intracellular delivery of both antigen and adjuvant to DCs. Here, we developed an advanced poly(d,l-lactide-co-glycolide) (PLGA)-NP encapsulating both ovalbumin (OVA) as a model antigen and polyinosinic-polycytidylic acid sodium salt (Toll-like receptor 3 ligand) as an adjuvant to increase intracellular delivery and promote DC maturation. The PLGA-NPs were taken up by DCs, and their uptake greatly facilitated major histocompatibility class I antigen presentation in vitro. Moreover, vaccination with PLGA-NP-treated DCs led to the generation of ovalbumin-specific CD8+ T cells, and the resulting antitumor efficacy was significantly increased in EG.7 and TC-1 tumor-bearing mice compared to control mice (P<0.01). Taken together, these findings demonstrated that the PLGA-NP platform may be an effective method for delivering tumor-specific antigens or adjuvants to DCs.

Keywords: PLGA nanoparticles; antigen delivery; cancer immunotherapy.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology
  • Dendritic Cells / immunology*
  • Female
  • Immunotherapy*
  • Lactic Acid / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*
  • Ovalbumin / immunology
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Thymoma / immunology
  • Thymoma / pathology
  • Thymoma / therapy*
  • Thymus Neoplasms / immunology
  • Thymus Neoplasms / pathology
  • Thymus Neoplasms / therapy
  • Toll-Like Receptor 3 / immunology*
  • Toll-Like Receptor 3 / metabolism

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Toll-Like Receptor 3
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Ovalbumin