Research

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

Marc Mansour¹ , Bill Pohajdak¹ , W Martin Kast² , Antar Fuentes-Ortega¹ , Ella Korets-Smith¹ , Genevieve M Weir¹ , Robert G Brown¹ and Pirouz Daftarian^1,3

¹  ImmunoVaccine Technologies Inc., Halifax, NS, Canada

²  Dept. of Molecular Microbiology & Immunology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA

³  Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada

author email corresponding author email

Journal of Translational Medicine 2007, 5:20doi:10.1186/1479-5876-5-20

Published:	23 April 2007

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.