Sultan, Kumai, and Nagato et al. showed that intravenous administration of a peptide vaccine resulted in a substantially more efficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) compared with subcutaneous administration. 24 hours after i.v. but not s.c. injection, antigen-presenting cells in the spleen and multiple lymph nodes strongly and broadly presented antigen. The CTL response was highly polyclonal and the magnitude of the CTL response positively correlated with tumor growth rate reduction. Palmitoylated, amphiphilic antigens were more immunogenic than long peptide formulations.
Vaccines consisting of synthetic peptides representing cytotoxic T-lymphocyte (CTL) epitopes have long been considered as a simple and cost-effective approach to treat cancer. However, the efficacy of these vaccines in the clinic in patients with measurable disease remains questionable. We believe that the poor performance of peptide vaccines is due to their inability to generate sufficiently large CTL responses that are required to have a positive impact against established tumors. Peptide vaccines to elicit CTLs in the clinic have routinely been administered in the same manner as vaccines designed to induce antibody responses: injected subcutaneously and in many instances using Freund's adjuvant. We report here that peptide vaccines and poly-ICLC adjuvant administered via the unconventional intravenous route of immunization generate substantially higher CTL responses as compared to conventional subcutaneous injections, resulting in more successful antitumor effects in mice. Furthermore, amphiphilic antigen constructs such as palmitoylated peptides were shown to be better immunogens than long peptide constructs, which now are in vogue in the clinic. The present findings if translated into the clinical setting could help dissipate the wide-spread skepticism of whether peptide vaccines will ever work to treat cancer.