Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax encapsulated CTL/T helper peptides

J Transl Med. 2007 Jun 7;5:26. doi: 10.1186/1479-5876-5-26.

Abstract

The incidence of cancer increases significantly in later life, yet few pre-clinical studies of cancer immunotherapy use mice of advanced age. A novel vaccine delivery platform (VacciMax,VM) is described that encapsulates antigens and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The therapeutic potential of VM-based vaccines administered as a single dose was tested in HLA-A2 transgenic mice of advanced age (48-58 weeks old) bearing large palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations contained a single peptide, a mixture of four peptides or the same four peptides linked together in a single long peptide. All VM formulations contained PADRE and CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil emulsion. VM-formulated vaccines containing the four peptides as a mixture or linked together in one long peptide eradicated 19-day old established tumors within 21 days of immunization. Peptide-specific cytotoxic cellular responses were confirmed by ELISPOT and intracellular staining for IFN-gamma producing CD8+ T cells. Mice rendered tumor-free by vaccination were re-challenged in the opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7 expressing tumor cell line. None of these mice developed tumors following the re-challenge. In summary, this report describes a VM-formulated therapeutic vaccine with the following unprecedented outcome: a) eradication of large tumors (> 700 mm3) b) in mice of advanced age c) in less than three weeks post-immunization d) following a single vaccination.

MeSH terms

  • Aging / immunology
  • Aging / pathology
  • Animals
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunization / instrumentation*
  • Interferon-gamma / metabolism
  • Intracellular Space / metabolism
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / pathology*
  • Peptides / immunology*
  • Spleen / cytology
  • Staining and Labeling
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Cancer Vaccines
  • Cytokines
  • Peptides
  • Interferon-gamma