Abstract
BackgroundS-588410 is a cancer peptide vaccine composed of five HLA-A*24:02-restricted epitope peptides derived from five cancer-testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, all of which are overexpressed in esophageal cancer. The aim of this study is to evaluate the effect of S-588410 on CD8 positive (+) T-lymphocytes in both blood and tumor tissue and PD-L1 expression in tumor tissue, by comparing of the specimens from before and after vaccination. MethodsHLA-A*24:02 positive patients (pts) with esophageal cancer who can receive the treatment more than 30 days before the surgery were eligible. S-588410 (1mg each of 5 peptides mixed with Montanide ISA 51 VG) was weekly injected subcutaneously. Blood and tumor tissue were collected for T cell receptors (TCR) repertoire analysis, multi-parameter immunohistochemistry and flow cytometry. Peptide-specific CTLs in PBMC were evaluated using ELISpot assay and tetramer assay. ResultsA total 15 pts were enrolled from Sep./2016 to Dec./2017. Pts received a median of 5 injections (range, 3-14) of S-588410. After vaccination, peptide-specific CTLs activity in PBMC were induced in all pts at least for 1 of 5 peptides. Multifunctional CD8+ T cells in PBMC were increased in 7 out of 12 pts and maintained in the other pts after vaccination. The densities of CD8+, CD8+GranzymeB+, CD8+PD1+ and PD-L1+ cell in tumor tissue after vaccination were higher than those before vaccination. Furthermore, in 6 out of 7 pts, TCRs identified from peptide-specific CTLs were present in both tumor tissue and PBMC after vaccination. ConclusionsVaccination of S-588410 induces CD8+/ CD8+PD1+ tumor-infiltrating cells and PD-L1 expression in esophageal cancer. These results suggest that S-588410 enhances tumor immunity and PD1/PD-L1 axis. Thus a combination of S-588410 with anti-PD1/PD-L1 antibody is expected to be more effective than monotherapy. Clinical trial identificationUMIN000023324. Legal entity responsible for the studyShionogi & Co., Ltd. FundingShionogi & Co., Ltd. DisclosureT. Kojima: Research grant / Funding (institution), Travel / Accommodation / Expenses, Sponsored initiated study: Shionogi; Research grant / Funding (institution), Sponsored initiated study: Ono Pharmaceutical; Research grant / Funding (institution), Sponsored initiated study: MSD; Research grant / Funding (institution), Sponsored initiated study: Oncolys BioPharma; Research grant / Funding (institution), Sponsored initiated study: Astellas Amgen BioPharma; Research grant / Funding (institution), Sponsored initiated study: Chugai; Research grant / Funding (institution), Sponsored initiated study: Parexel. T. Nakatsura: Advisory / Consultancy, Compensation for IDMC: Shionogi. K. Kato: Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Merck Serono. T. Hikichi: Full / Part-time employment: Cancer Precision Medicine. S. Yoshimura: Full / Part-time employment: Cancer Precision Medicine. T. Nakagawa: Full / Part-time employment: Shionogi. M. Furukawa: Full / Part-time employment: Shionogi. K. Stoeber: Full / Part-time employment: Shionogi. M. Nagira: Full / Part-time employment: Shionogi. N. Ide: Full / Part-time employment: Shionogi. All other authors have declared no conflicts of interest.
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