Relevance of the tumor antigen in the validation of three vaccination strategies for melanoma

Citation
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
Citations number
34
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
5
Year of publication
2000
Pages
2651 - 2656
Database
ISI
SICI code
0022-1767(20000901)165:5<2651:ROTTAI>2.0.ZU;2-A
Abstract
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.