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Open Access 01-08-2020 | Shock | Clinical Trial Report

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial

Authors: Masao Nakajima, Shoichi Hazama, Koji Tamada, Keiko Udaka, Yasunobu Kouki, Toshinari Uematsu, Hideki Arima, Akira Saito, Shun Doi, Hiroto Matsui, Yoshitaro Shindo, Satoshi Matsukuma, Shinsuke Kanekiyo, Yukio Tokumitsu, Shinobu Tomochika, Michihisa Iida, Shin Yoshida, Yuki Nakagami, Nobuaki Suzuki, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Tomio Ueno, Hiroaki Nagano

Published in: Cancer Immunology, Immunotherapy | Issue 8/2020

Abstract

Background

This phase I study aimed to evaluate the safety, peptide-specific immune responses, and anti-tumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers.

Methods

HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system. The peptides were intradermally administered with combined adjuvants on a weekly basis. This study was a phase I dose escalation clinical trial, which was carried out in a three patients’ cohort; in total, 11 patients were enrolled for the recommended dose.

Results

Seventeen patients received this vaccination therapy without dose-limiting toxicity. All treatment-related adverse events were of grades 1 to 2. Peptide-specific CTL induction by HSP70 and GPC3 proteins was observed in 11 (64.7%) and 13 (76.5%) cases, respectively, regardless of the HLA type. Serum tumor marker levels were decreased in 10 cases (58.8%). Immunological analysis using PBMCs indicated that patients receiving dose level 3 presented with significantly reduced T cell immunoglobulin and mucin-domain containing-3 (TIM3)-expressing CD4 + T cells after one course of treatment. PD-1 or TIM3-expressing CD4 + T cells and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)-expressing CD8 + T cells in PBMCs before vaccination were negative predictive factors for survival.

Conclusions

This novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers.

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Title: A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial
Authors: Masao Nakajima
Shoichi Hazama
Koji Tamada
Keiko Udaka
Yasunobu Kouki
Toshinari Uematsu
Hideki Arima
Akira Saito
Shun Doi
Hiroto Matsui
Yoshitaro Shindo
Satoshi Matsukuma
Shinsuke Kanekiyo
Yukio Tokumitsu
Shinobu Tomochika
Michihisa Iida
Shin Yoshida
Yuki Nakagami
Nobuaki Suzuki
Shigeru Takeda
Shigeru Yamamoto
Shigefumi Yoshino
Tomio Ueno
Hiroaki Nagano
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Shock
Cancer Biomarker
Vaccination
Shock
Published in: Cancer Immunology, Immunotherapy / Issue 8/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02518-7

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Abstract

Background

Methods

Results

Conclusions

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