Efficient Eradication of Established Tumors in Mice with Cationic Liposome-Based Synthetic Long-Peptide Vaccines

Cancer Immunol Res. 2017 Mar;5(3):222-233. doi: 10.1158/2326-6066.CIR-16-0283. Epub 2017 Jan 31.

Abstract

Therapeutic vaccination with synthetic long peptides (SLP) can be clinically effective against HPV-induced premalignant lesions; however, their efficiency in established malignant lesions leaves room for improvement. Here, we report the high therapeutic potency of cationic liposomes loaded with well-defined tumor-specific SLPs and a TLR3 ligand as adjuvant. The cationic particles, with an average size of 160 nm, could strongly activate functional, antigen-specific CD8+ and CD4+ T cells and induced in vivo cytotoxicity against target cells after intradermal vaccination. At a low dose (1 nmol) of SLP, our liposomal formulations significantly controlled tumor outgrowth in two independent models (melanoma and HPV-induced tumors) and even cured 75%-100% of mice of their large established tumors. Cured mice were fully protected from a second challenge with an otherwise lethal dose of tumor cells, indicating the potential of liposomal SLP in the formulation of powerful vaccines for cancer immunotherapy. Cancer Immunol Res; 5(3); 222-33. ©2017 AACR.

MeSH terms

  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Immunization
  • Liposomes*
  • Melanoma, Experimental
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / mortality
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Papillomavirus E7 Proteins / chemistry
  • Papillomavirus E7 Proteins / immunology
  • Poly I-C
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology*

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Liposomes
  • Papillomavirus E7 Proteins
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Poly I-C