Mayurkumar Kalariya1, Srinivas Ganta, Mansoor Amiji. 1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, Massachusetts 02115, USA.
Abstract
PURPOSE: To develop a multi-compartmental vaccine delivery system for safe and efficient delivery of the gp100 peptide antigen in melanoma immunotherapy. METHODS: Water-in-oil-in-water (W/O/W) multiple emulsion-based multi-compartmental vaccine delivery system containing the gp100 peptide was prepared by a two-step emulsification method. In vivo prophylactic and active immunization effectiveness of the novel squalane oil-containing gp100 vaccine was evaluated in the murine B16 melanoma model and compared with that of an incomplete Freund's adjuvant (IFA)-based vaccine. RESULTS: Morphological evaluation of the W/O/W multiple emulsions showed that the oil-droplets were homogenously dispersed with the gp100 peptide encapsulated in an inner aqueous phase. Immunization with the gp100 peptide delivered in the W/O/W multiple emulsions-based vaccine resulted in increased protection against tumor challenge compared to IFA-based vaccine (p < 0.05, n = 8) signifying induction of enhanced anti-tumor immunity. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation and local infiltration of antigen specific cytotoxic T-lymphocytes into and/or surrounding the tumor mass. Moreover, the newly developed vaccine formulation did not induce any overt systemic toxicity. CONCLUSION: Novel W/O/W multiple emulsions-based vaccine efficiently delivers the gp100 peptide antigen to induce cell-mediated anti-tumor immunity and offers an alternate, safe vaccine delivery system.
PURPOSE: To develop a multi-compartmental vaccine delivery system for safe and efficient delivery of the gp100 peptide antigen in melanoma immunotherapy. METHODS:Water-in-oil-in-water (W/O/W) multiple emulsion-based multi-compartmental vaccine delivery system containing the gp100 peptide was prepared by a two-step emulsification method. In vivo prophylactic and active immunization effectiveness of the novel squalane oil-containing gp100 vaccine was evaluated in the murine B16 melanoma model and compared with that of an incomplete Freund's adjuvant (IFA)-based vaccine. RESULTS: Morphological evaluation of the W/O/W multiple emulsions showed that the oil-droplets were homogenously dispersed with the gp100 peptide encapsulated in an inner aqueous phase. Immunization with the gp100 peptide delivered in the W/O/W multiple emulsions-based vaccine resulted in increased protection against tumor challenge compared to IFA-based vaccine (p < 0.05, n = 8) signifying induction of enhanced anti-tumor immunity. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation and local infiltration of antigen specific cytotoxic T-lymphocytes into and/or surrounding the tumor mass. Moreover, the newly developed vaccine formulation did not induce any overt systemic toxicity. CONCLUSION: Novel W/O/W multiple emulsions-based vaccine efficiently delivers the gp100 peptide antigen to induce cell-mediated anti-tumor immunity and offers an alternate, safe vaccine delivery system.
Authors: Friedrich H Schmitz-Winnenthal; Christine Volk; Kaspar Z'graggen; Luis Galindo; Daniel Nummer; Yvonne Ziouta; Marianna Bucur; Jürgen Weitz; Volker Schirrmacher; Markus W Büchler; Philipp Beckhove Journal: Cancer Res Date: 2005-11-01 Impact factor: 12.701