Effect of TLR ligands co-encapsulated with multiepitopic antigen in nanoliposomes targeted to human DCs via Fc receptor for cancer vaccines

Immunobiology. 2017 Nov;222(11):989-997. doi: 10.1016/j.imbio.2017.06.002. Epub 2017 Jun 10.

Abstract

Nanoliposomes (NLs) hold promise as new highly specific nanomedicine for anti-tumor vaccines, since they could be targeted to specific receptors on dendritic cell (DC) to induce maturation and activation and increase the anti-tumor immune response. Here we studied a NLs formulation targeted or not to FcR (the receptor for the IgG Fc fragment) for the treatment of androgen-responsive prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) peptide (B- and T-cell epitopes), in tandem with a tetanus toxoid T-helper epitope (830-844 region) and several TLR (Toll-Like Receptor) ligands as adjuvants were co-encapsulated. Specific uptake in vitro of LHRH-TT liposomes targeted to the FcRs of human DCs was enhanced. DC maturation/activation, cytokine production and lymphocyte activation were consistently higher in targeted than non-targeted liposomes. Similar increase was observed as more adjuvants were administrated. Targeting to specific receptor and co-encapsulation of several TLR adjuvants are essential factors for the immune response in peptide based liposome vaccine.

Keywords: Cancer vaccines; Delivery system; Dendritic cells; Immunotherapeutic vaccines; Peptide vaccines; Targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Drug Compounding
  • Epitopes, B-Lymphocyte / genetics*
  • Epitopes, T-Lymphocyte / genetics*
  • Gonadotropin-Releasing Hormone / genetics*
  • Gonadotropin-Releasing Hormone / immunology
  • Humans
  • Immunity
  • Liposomes / chemistry
  • Liposomes / immunology*
  • Male
  • Nanostructures / chemistry
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / prevention & control
  • Receptors, Fc / metabolism
  • Self Tolerance
  • Tetanus Toxin / genetics
  • Toll-Like Receptors / agonists

Substances

  • Androgens
  • Cancer Vaccines
  • Cytokines
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Liposomes
  • Receptors, Fc
  • Tetanus Toxin
  • Toll-Like Receptors
  • Gonadotropin-Releasing Hormone