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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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
Externally publishedYes

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Peptide T
Experimental Melanomas
Tumors
Vaccination
Peptides
Vaccines
Neoplasms
Antigens
Bearings (structural)
Therapeutics
Neoplasm Antigens
Liposomes
Epitopes
Melanoma
Melanoma-Specific Antigens
Enzyme-Linked Immunospot Assay
Tumor Suppressor Protein p53
Inbred C57BL Mouse

ASJC Scopus subject areas

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

Cite this

Mansour, M., Pohajdak, B., Kast, W. M., Fuentes-Ortega, A., Korets-Smith, E., Weir, G. M., ... 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

Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax®. / Mansour, Marc; Pohajdak, Bill; Kast, W. Martin; Fuentes-Ortega, Antar; Korets-Smith, Ella; Weir, Genevieve M.; Brown, Robert G.; Daftarian, Pirouz.

In: Journal of Translational Medicine, Vol. 5, 20, 23.04.2007.

Research output: Contribution to journalArticle

Mansour, M, Pohajdak, B, Kast, WM, Fuentes-Ortega, A, Korets-Smith, E, Weir, GM, Brown, RG & 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, vol. 5, 20. https://doi.org/10.1186/1479-5876-5-20
Mansour, Marc ; Pohajdak, Bill ; Kast, W. Martin ; Fuentes-Ortega, Antar ; Korets-Smith, Ella ; Weir, Genevieve M. ; Brown, Robert G. ; Daftarian, Pirouz. / Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax®. In: Journal of Translational Medicine. 2007 ; Vol. 5.
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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{\circledR} (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.",
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