We previously identified a
human leukocyte antigen (HLA)-A24-restricted antigenic
peptide, survivin-2B80-88, recognized by CD8+ cytotoxic T lymphocytes (CTL). Subsequently, we attempted clinical trials with this
epitope peptide alone for some
malignancies, resulting in clinical and immunological responses, although their potential was not strong enough for routine clinical use as a
cancer vaccine. In the current study, to assess whether immunogenicity of the survivin-2B80-88
peptide could be enhanced with other vaccination protocols, we performed clinical trials in advanced
colon cancer patients with two vaccination protocols: (i) survivin-2B80-88 plus
incomplete Freund's adjuvant (IFA); and (ii) survivin-2B80-88 plus IFA and a
type-I interferon (IFN), IFNα. Our data clearly indicated that, although the effect of survivin-2B80-88 plus IFA was not significantly different from that with survivin-2B80-88 alone, treatment with the vaccination protocol of survivin-2B80-88 plus IFA and IFNα resulted in clinical improvement and enhanced immunological responses of patients. Tetramer analysis of survivin-2B80-88
peptide-specific CTL demonstrated that such CTL were increased at least twofold after vaccination with this protocol in four of eight patients. In these patients,
enzyme-linked
immunosorbent spot (ELISPOT) results were also enhanced. Subsequent study of single-cell clone separation by cell sorting of
peptide-specific CTL showed that each CTL clone was indeed not only
peptide-specific but also cytotoxic against human
cancer cells in the context of the expression of both
HLA-A24 and
survivin molecules. Taken together, these results indicate that vaccination of
colon cancer patients with survivin-2B80-88 plus IFA and IFNα can be considered to be a very potent immunotherapeutic regimen, and that this protocol might work for other
cancers.