Efficient delivery of tumour-associated
antigens to appropriate cellular compartments of antigen-presenting cells is of prime importance for the induction of potent, cell-mediated antitumour immune responses. We have designed novel multivalent liposomal constructs that co-deliver the p63-71 cytotoxic T Lymphocyte
epitope derived from human ErbB2 (HER2), and
HA307-319, a T-helper (Th)
epitope derived from
influenza haemagglutinin. Both
peptides were conjugated to the surface of
liposomes via a Pam3CSS anchor, a synthetic
lipopeptide with potent adjuvant activity. In a murine model system, vaccination with these constructs completely protected BALB/c mice from subsequent s.c. challenge with ErbB2-expressing, but not ErbB2-negative, murine
renal carcinoma (Renca) cells, indicating the induction of potent,
antigen-specific immune responses. I.v. re-challenge of tumour-free animals 2 months after the first tumour cell inoculation did not result in the formation of lung tumour nodules, suggesting that long-lasting, systemic immunity had been induced. While still protecting the majority of vaccinated mice, a liposomal construct lacking the Th
epitope was less effective than the diepitope construct, also correlating with a lower number of CD8+ IFN-gamma+ T-cells identified upon ex vivo
peptide restimulation of splenocytes from vaccinated animals. Importantly, in a therapeutic setting treatment with the liposomal
vaccines resulted in cures in the majority of tumour-bearing mice and delayed tumour growth in the remaining ones. Our results demonstrate that liposomal constructs which combine Tc and Th
peptide antigens and
lipopeptide adjuvants can induce efficient,
antigen-specific antitumour immunity, and represent promising synthetic delivery systems for the design of specific antitumour
vaccines.