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.
Resources from the same session
3524 - Cabazitaxel For Octogenarian Patients With Metastatic Castration-Resistant Prostate Cancer (MCRPC).
Presenter: Paolo Tralongo
Session: Poster Display session 3
Resources:
Abstract
5637 - External Validation of a Prognostic Score in First-Line Metastastic Castration-Resistant Prostate Cancer (mCRPC)
Presenter: David Lorente
Session: Poster Display session 3
Resources:
Abstract
3228 - Treatment outcomes of 3rd treatment in a real-world metastatic castration resistant prostate cancer (mCRPC) population: results from the Dutch CAPRI-registry
Presenter: Jessica Notohardjo
Session: Poster Display session 3
Resources:
Abstract
4695 - Pelvic lymph node dissection and its extent on survival benefit in prostate cancer patients with a risk of lymph node invasion>5%: a propensity score matching analysis from SEER database
Presenter: Junru Chen
Session: Poster Display session 3
Resources:
Abstract
4438 - Multi-institutional evaluation of therapeutic management for oligometastatic cancer prostate recurrence with choline-PET/CT
Presenter: Morgane Guibert-broudic
Session: Poster Display session 3
Resources:
Abstract
4574 - Safety of new androgen receptor inhibitors (ARi) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC): a network meta-analysis of randomized controlled trials (RCT)
Presenter: Amelia Altavilla
Session: Poster Display session 3
Resources:
Abstract
3816 - Real-world use of radium-223 for treatment of metastatic castration resistant-prostate cancer (mCRPC): results from the Dutch CAPRI registry
Presenter: Malou Kuppen
Session: Poster Display session 3
Resources:
Abstract
5180 - A phase 2a study of radium-223 dichloride (Ra-223) alone or in combination with abiraterone acetate or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Daniel Petrylak
Session: Poster Display session 3
Resources:
Abstract
1067 - Adding ADT to PSMA-PET/CT-guided SBRT for oligometastatic prostate cancer improves distant progression-free survival
Presenter: Carole Mercier
Session: Poster Display session 3
Resources:
Abstract
5529 - Safety and efficacy of Ac-225-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) after failure of Lu-177-PSMA
Presenter: Robert Tauber
Session: Poster Display session 3
Resources:
Abstract