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

• Main Authors: MacDonald Lisa, Korets-Smith Ella, Fuentes-Ortega Antar, Pohajdak Bill, Mansour Marc, Daftarian Pirouz M, Weir Genevieve, Brown Robert G, Kast W Martin
• Format: Article
• Language: English
• Published: BMC 2007-06-01
• Series: Journal of Translational Medicine
• Online Access: http://www.translational-medicine.com/content/5/1/26

<p>Abstract</p> <p>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.</p>