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
Year: 2020
Type: article
Study design: Clinical Trial
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.
Source: Cancer Immunology Immunotherapy
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
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,860
Awards: G1650677228, Identification for biomarkers in cancer peptide vaccine therapy with immune checkpoint inhibitors, Elucidation of immune suppression using tumor-infiltrating lymphocytes in perioperative immunotherapy for patients with hepatocellular carcinoma, Research for novel biomarkers and therapeutic targets related to cancer microenvironment in pancreatic cancer, Rational design of the next-generation peptide immunotherapy which exploits tumor endothelial cells as an APC., Identification of HLA-binding peptides of liver cnancer stem cells, Deployment to personalized medicine targeting pancreatic cancer stem cells and tumor microenvironment
OpenAlex ID: W3013632761