Intratumoral delivery of antigen with complement C3-bound liposomes reduces tumor growth in mice

Nanomedicine. 2019 Jun:18:326-335. doi: 10.1016/j.nano.2018.10.009. Epub 2018 Nov 9.

Abstract

Antigen presenting cells (APCs) initiate the immune response against cancer by engulfing and presenting tumor antigens to T cells. Our lab has recently developed a liposomal nanoparticle that binds complement C3 proteins, allowing it to bind to the complement C3 receptors of APCs and directly deliver antigenic peptides. APCs were shown to internalize and process complement C3-bound liposomes containing ovalbumin (OVA), resulting in a significant increase in activated T cells that recognize OVA. Mice bearing A20-OVA lymphoma tumors were treated with OVA-loaded C3-liposomes, which led to reduced tumor growth in both treated and distal tumors in all mice. Peripheral blood from treated mice had a lower percentage of immunosuppressive myeloid derived suppressor cells (MDSCs), a higher percentage of B cells, and increased anti-OVA IgG1 levels compared to control mice. These results indicate that C3-liposome delivery of tumor antigen to APCs initiates a potent and systemic antitumor immune response.

Keywords: Antigen-presenting cells; Cancer immunotherapy; Complement C3; Nanoparticle; Targeted delivery; Tumor antigen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Complement C3 / metabolism*
  • Dendritic Cells / metabolism
  • Endocytosis
  • Humans
  • Immunoglobulin G / blood
  • Liposomes / chemistry*
  • Liver / enzymology
  • Lymphocyte Activation / immunology
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid-Derived Suppressor Cells / metabolism
  • Neoplasms / blood
  • Neoplasms / pathology*
  • Ovalbumin / administration & dosage*
  • T-Lymphocytes / immunology
  • Tumor Burden

Substances

  • Complement C3
  • Immunoglobulin G
  • Liposomes
  • Ovalbumin