Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax®

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

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34 Scopus citations

Abstract

Background: Melanoma tumors are known to express antigens that usually induce weak immune responses of short duration. Expression of both tumor-associated antigens p53 and TRP2 by melanoma cells raises the possibility of simultaneously targeting more than one antigen in a therapeutic vaccine. In this report, we show that VacciMax® (VM), a novel liposome-based vaccine delivery platform, can increase the immunogenicity of melanoma associated antigens, resulting in tumor elimination. Methods: C57BL/6 mice bearing B16-F10 melanoma tumors were vaccinated subcutaneously 6 days post tumor implantation with a mixture of synthetic peptides (modified p53: 232-240, TRP-2: 181-188 and PADRE) and CpG. Tumor growth was monitored and antigen-specific splenocyte responses were assayed by ELISPOT. Results: Vaccine formulated in VM increased the number of both TRP2- and p53-specific IFN-γ producing splenocytes following a single vaccination. Vaccine formulated without VM resulted only in enhanced IFN-γ producing splenocytes to one CTL epitopes (TRP2:180-188), suggesting that VM overcomes antigen dominance and enhances immunogenicity of multiple epitopes. Vaccination of mice bearing 6-day old B16-F10 tumors with both TRP2 and p53-peptides formulated in VM successfully eradicated tumors in all mice. A control vaccine which contained all ingredients except liposomes resulted in eradication of tumors in no more than 20% of mice. Conclusion: A single administration of VM is capable of inducing an effective CTL response to multiple tumor-associated antigens. The responses generated were able to reject 6-day old B16-F10 tumors.

Original languageEnglish (US)
Article number20
JournalJournal of translational medicine
Volume5
DOIs
StatePublished - Apr 23 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Mansour, M., Pohajdak, B., Kast, W. M., Fuentes-Ortega, A., Korets-Smith, E., Weir, G. M., Brown, R. G., & Daftarian, P. (2007). Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax®. Journal of translational medicine, 5, [20]. https://doi.org/10.1186/1479-5876-5-20