Abstract 2320
Background
S-588410 is a cancer peptide vaccine composed of 5 HLA-A*24:02-restricted peptides derived from 5 cancer-testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, all of which have been found to be upregulated in esophageal cancer. The aim of this study is to evaluate the effects of S-588410 on the number of tumor-infiltrating CD8-positive lymphocytes (TIL) and PD-L1 expression in the tumor tissue before and after the short-term treatment with S-588410 in the pre-surgical treatment.
Methods
HLA-A*24:02-positive patients (pts) with esophageal cancer who can start the treatment more than 30 days prior to the surgery were eligible. S-588410 was injected subcutaneously once weekly, 5 times or more in total. Tumor tissues of pre- and post-treatment were collected for immunohistochemistry (IHC) analysis for target antigens, CD8, PD-L1 and HLA class I. Peptide-specific CTLs in PBMC were evaluated using ELISpot assay.
Results
As Apr 13, 2018, total 15 pts were enrolled and tumor tissues of the first half of the pts, 8 pts were analyzed. 8 pts received 3 to 6 injections of S-588410. All 5 antigens and HLA class I on tumor tissues were detected in all pts except for one whose tumor expressed 4 target antigens. CTL activity circulating in blood markedly increased in all 8 pts at least for 1 of 5 peptides. IHC analysis demonstrated that TIL density and PD-L1 expression on post-treatment tissues clearly increased compared to the baseline; CD8+ TIL density at baseline was ≤ 1% in 5 pts and 1%-10% in 3 pts and that for post-treatment 1%-10% in 2 pts, 10%-50% in 6 pts, and PD-L1 expression at base line was ≤ 1% in 7 pts and 1%-5% in one patient and that for post-treatment was ≤ 1% in one patient, 1%-5% in 4 pts and 5%-50% in 3 pts.
Conclusions
The short-term treatment with S-588410 generated peptide-specific CTL and markedly increased CD8+ TIL density and PD-L1 expression on tumor tissue of esophageal cancer pts. These interim results suggest that the combination of S-588410 with anti-PD-1/PD-L1 antibody is expected to be more effective than monotherapy, particularly in pts with low TIL/PD-L1 status.
Clinical trial identification
UMIN000023324.
Legal entity responsible for the study
Shionogi & Co., Ltd.
Funding
Shionogi & Co., Ltd.
Editorial Acknowledgement
Disclosure
T. Kojima: Travel grants: Shionogi & Co., Ltd.; Grants: Ono Pharmaceutical, MSD, Oncolys BioPharma, Astellas Amgen BioPharama. M. Nagira, N. Ide, K. Stoeber, A. Arimura: Employee: Shionogi & Co., Ltd. All other authors have declared no conflicts of interest.
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