2. Academic Validation
  3. Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients

Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients

  • Cancer Immunol Immunother. 2020 Nov;69(11):2247-2257. doi: 10.1007/s00262-020-02619-3.
H Daiko 1,  T Marafioti 2,  T Fujiwara 3,  Y Shirakawa 3,  T Nakatsura 4,  K Kato 5,  I Puccio 2,  T Hikichi 6,  S Yoshimura 6,  T Nakagawa 7,  M Furukawa 8,  K Stoeber 9,  M Nagira 7,  N Ide 10,  T Kojima 11
Affiliations

Affiliations

  • 1 Esophageal Surgery Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. [email protected].
  • 2 Department of Cellular Pathology, University College London Hospital, London, UK.
  • 3 Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • 4 Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
  • 5 Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
  • 6 R&D Department, Cancer Precision Medicine, Inc., Kawasaki, Japan.
  • 7 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., Toyonaka, Japan.
  • 8 Biostatistics Department, Shionogi & Co., Ltd., Osaka, Japan.
  • 9 Business Development, Shionogi & Co., Ltd., London, UK.
  • 10 Project Management Department, Shionogi & Co., Ltd., Osaka, Japan.
  • 11 Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
PMID: 32500232 DOI: 10.1007/s00262-020-02619-3
Abstract

Cancer vaccines induce cancer-specific T-cells capable of eradicating Cancer cells. The impact of Cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted Peptides derived from five Cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal Cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal Cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five Peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal Cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 Antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.

Keywords

Cancer peptide vaccine; Esophageal cancer; PD-1; PD-L1; Tumor-infiltrating lymphocytes.

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