A multiantigen multipeptide
vaccine, targeting
proteins expressed in preinvasive breast lesions, can stimulate type I CD4(+) T cells which have been shown to be deficient in both patients with
breast cancer and mice that develop mammary
tumors. Transgenic mice (TgMMTV-neu) were immunized with a multiantigen
peptide vaccine specific for neu,
insulin-like growth factor-binding protein 2 and
insulin-like growth factor receptor-I at a time when some of the animals already had preinvasive lesions (18 weeks of age). Although immunization with each individual
antigen was partially effective in inhibiting
tumor growth, immunization with the multiantigen
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 with 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. Although 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 the mice showed no pathologic evidence of
carcinomas at one year. The
vaccine also demonstrated significant clinical efficacy in an additional transgenic model of
breast cancer (TgC3(I)-Tag). Chemoimmunoprevention combinations may be an effective approach to
breast cancer prevention even when the
vaccine is administered in the presence of subclinical disease.