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

Pirouz M. Daftarian, Marc Mansour, Bill Pohajdak, Antar Fuentes-Ortega, Ella Korets-Smith, Lisa MacDonald, Genevieve Weir, Robert G. Brown, W. Martin Kast

Research output: Contribution to journalArticle

29 Citations (Scopus)

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-γ 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.

Original languageEnglish (US)
Article number26
JournalJournal of Translational Medicine
Volume5
DOIs
StatePublished - Jun 7 2007
Externally publishedYes

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Peptide T
Immunization
Human papillomavirus 16
Tumors
Peptides
Vaccines
Neoplasms
HLA-A2 Antigen
Emulsions
Oils
Vaccination
Bearings (structural)
Cells
Enzyme-Linked Immunospot Assay
T-cells
Water
Tumor Cell Line
varespladib methyl
Liposomes
Immunotherapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Daftarian, P. M., Mansour, M., Pohajdak, B., Fuentes-Ortega, A., Korets-Smith, E., MacDonald, L., ... Kast, W. M. (2007). Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides. Journal of Translational Medicine, 5, [26]. https://doi.org/10.1186/1479-5876-5-26

Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides. / Daftarian, Pirouz M.; Mansour, Marc; Pohajdak, Bill; Fuentes-Ortega, Antar; Korets-Smith, Ella; MacDonald, Lisa; Weir, Genevieve; Brown, Robert G.; Kast, W. Martin.

In: Journal of Translational Medicine, Vol. 5, 26, 07.06.2007.

Research output: Contribution to journalArticle

Daftarian, PM, Mansour, M, Pohajdak, B, Fuentes-Ortega, A, Korets-Smith, E, MacDonald, L, Weir, G, Brown, RG & Kast, WM 2007, 'Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides', Journal of Translational Medicine, vol. 5, 26. https://doi.org/10.1186/1479-5876-5-26
Daftarian, Pirouz M. ; Mansour, Marc ; Pohajdak, Bill ; Fuentes-Ortega, Antar ; Korets-Smith, Ella ; MacDonald, Lisa ; Weir, Genevieve ; Brown, Robert G. ; Kast, W. Martin. / Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides. In: Journal of Translational Medicine. 2007 ; Vol. 5.
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