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Poster Display session 3

1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Presenters

Takashi Kojima

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

T. Kojima1, T. Marafioti2, T. Fujiwara3, Y. Shirakawa3, T. Nakatsura4, K. Kato5, I. Puccio2, T. Hikichi6, S. Yoshimura6, T. Nakagawa7, M. Furukawa8, K. Stoeber9, M. Nagira7, N. Ide8, H. Daiko10

Author affiliations

  • 1 Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2 Department Of Cellular Pathology, University College London Hospital, London/GB
  • 3 Gastroenterological Surgery, Okayama University Hospital, Okayama/JP
  • 4 Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa/JP
  • 5 Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo/JP
  • 6 R&d Department, Cancer Precision Medicine, Inc., Kawasaki/JP
  • 7 Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd, Toyonaka/JP
  • 8 Project Management Department, Shionogi & Co., Ltd, Osaka/JP
  • 9 Business Development, Shionogi & Co., Ltd, London/GB
  • 10 Esophageal Surgery Division, National Cancer Center Hospital, 1040045 - Tokyo/JP

Resources

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Abstract 1845

Background

S-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.

Methods

HLA-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 (1 mg 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.

Results

A 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.

Conclusions

Vaccination 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 identification

UMIN000023324.

Editorial acknowledgement

Legal entity responsible for the study

Shionogi & Co., Ltd.

Funding

Shionogi & Co., Ltd.

Disclosure

T. 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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