Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax.
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-gamma producing splenocytes following a single vaccination. Vaccine formulated without VM resulted only in enhanced IFN-gamma 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.


CONCLUSIONS
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.
Mansour
Marc
M
ImmunoVaccine Technologies Inc., Halifax, NS, Canada. mm.ivt@immunovaccine.com
Pohajdak
Bill
B
Kast
W Martin
WM
Fuentes-Ortega
Antar
A
Korets-Smith
Ella
E
Weir
Genevieve M
GM
Brown
Robert G
RG
Daftarian
Pirouz
P
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014611:Vaccination / Q000295:instrumentation*
D019496:Cancer Vaccines; D010455:Peptides; D007371:Interferon-gamma