Abstract
BackgroundMelanoma 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.MethodsC57BL/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.ResultsVaccine 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.ConclusionA 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.
Highlights
Melanoma tumors are known to express antigens that usually induce weak immune responses of short duration
Previous studies using two mouse models have demonstrated that peptide-based vaccines delivered using VacciMax® (VM) can eradicate human papillomavirus (HPV) 16 induced tumors [1,2]
The identification of tumor-associated antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL) has led to the development of specific anti-tumor immunotherapies
Summary
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. Previous studies using two mouse models have demonstrated that peptide-based vaccines delivered using VacciMax® (VM) can eradicate human papillomavirus (HPV) 16 induced tumors [1,2]. The aim of the present study is to use VM in a therapeutic vaccine to treat C57BL/6 mice bearing B16-F10 melanoma tumors Eradication of both HPV 16 and B16-F10 melanoma tumors would suggest that VM could enhance various therapeutic cancer vaccines. VM is a liposome-based antigen delivery platform which we have shown to be effective in both preventing and eradicating established HPV 16-induced tumors in mouse models [1,2]. This report examines the use of VM in a melanoma mouse model
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