M. Bellone et al., Relevance of the tumor antigen in the validation of three vaccination strategies for melanoma, J IMMUNOL, 165(5), 2000, pp. 2651-2656
Many preclinical studies of cancer immunotherapy are based on the testing o
f a single vaccination strategy in several tumor models. Moreover, most of
those studies used xenogeneic Ags, which, owing to their high immunogenicit
y, may not represent realistic models for the validation of cancer immunoth
erapies, To address these issues, we compared the vaccination efficacy of t
hree well established strategies (i.e., naked DNA; peptide-pulsed dendritic
cells (DC), or a mixture of peptide and the Escherichia coli toxin LTR72)
using the xenogeneic OVA or the naturally expressed tyrosinase-related prot
ein 2 (TRP-2) tumor Ag in the B16 melanoma model. C57BL/6 mice received one
to three s.c. injections of peptide-pulsed DC or DNA, or one to four mucos
al administrations of peptide-toxin mixture. One to 2 wk later, the animals
were challenged s.c. with B16 or B16 cells expressing OVA (B16-OVA), Vacci
nation of mice with OVA induced in all cases melanoma-specific CTL and prot
ection against B16-OVA, When TRP-2, was used, all three vaccines elicited B
16-specific CTL, but only DC pulsed with the immunodominant T cell epitope
TRP-2(181-188) allowed protection against B16. Even more importantly, a vac
cination regimen with TRP-2-pulsed DC, started 24 h after the injection of
a lethal number of B16 cells, caused a therapeutic effect in 60% of the cha
llenged animals. Our results strongly emphasize the relevance of the tumor
Ag in the definition of immunotherapeutic strategies for cancer, and suppor
t the use of peptide-pulsed DC as cancer vaccine in humans.