A multi-antigen vaccine targeting neu, IGFBP-2 and IGF-IR prevents tumor progression in mice with pre-invasive breast disease
Menée sur des modèles murins transgéniques, cette étude montre qu'un vaccin multi-antigène ciblant NEU, IGFBP-2 et IGF-IR peut prévenir la progression de lésions mammaires pré-invasives
A multi-antigen multi-peptide vaccine, targeting proteins expressed in pre-invasive breast lesions, can stimulate Type I CD4+ T-cells which have been shown to be deficient in both breast cancer patients and mice that develop mammary tumors. Transgenic mice (TgMMTV-neu) were immunized with a multi-antigen peptide vaccine specific for neu, IGFBP-2 and IGF-IR at a time when some of the animals already had pre-invasive lesions (18 weeks of age). While immunization with each individual antigen was partially effective in inhibiting tumor growth, immunization with the multi-antigen vaccine was highly effective, blocking development of palpable lesions in 65% of mice and slowing tumor growth in the infrequent palpable tumors which did arise. Protection was mediated by CD4+ T-cells and the few slow-growing tumors that did develop demonstrated a significant increase in intratumoral CD8+ T-cells as compared to controls (p=0.0007). We also combined the vaccine with agents that were, by themselves, partially effective inhibitors of tumor progression in this model; lapatinib and the RXR agonist bexarotene. While the combination of lapatinib and vaccination performed similarly to vaccination alone (p=0.735), bexarotene and vaccination significantly enhanced disease free survival (p<0.0001) and approximately 90% of mice showed no pathologic evidence of carcinomas at 1 year. The vaccine also demonstrated significant clinical efficacy in an additional transgenic model of breast cancer (TgC3(I)-Tag). Chemo-immunoprevention combinations may be an effective approach to breast cancer prevention even when the vaccine is administered in the presence of subclinical disease.