Phase I study of a novel therapeutic vaccine as perioperative treatment for patients with surgically resectable hepatocellular carcinoma: The YCP02 trial

Masao Nakajima, Shoichi Hazama, Yukio Tokumitsu, Yoshitaro Shindo, Hiroto Matsui, Satoshi Matsukuma, Yuki Nakagami, Koji Tamada, Keiko Udaka, Michiie Sakamoto, Akira Saito, Yasunari Kouki, Toshinari Uematsu, Ming Xu, Michihisa Iida, Ryouichi Tsunedomi, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, Shun DoiHiroaki Nagano

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Aim: Developing effective adjuvant therapies is essential for improving the surgical outcomes in patients with hepatocellular carcinoma (HCC). Immunotherapy against HCC has become a promising strategy; however, only approximately 30% of all HCC patients respond to immunotherapy. Previously, we generated the novel therapeutic vaccine comprising multi-human leukocyte antigen-binding heat shock protein 70/glypican-3 peptides with a novel adjuvant combination of hLAG-3Ig and poly-ICLC. We also confirmed the safety of this vaccination therapy, as well as its capacity for the effective induction of immune responses in a previous clinical trial. Methods: In this phase I study, we administered this vaccine intradermally six times before surgery, and 10 times after surgery to patients with untreated, surgically resectable HCC (stage II to IVa). The primary end-points of this study were the safety and feasibility of this treatment. We also analyzed the resected tumor specimens pathologically using hematoxylin–eosin staining and immunohistochemistry for heat shock protein 70, glypican 3, CD8 and programmed death-1. Results: A total of 20 human leukocyte antigen-matched patients received this vaccination therapy with an acceptable side-effect profile. All patients underwent planned surgery without vaccination-related delay. Immunohistochemical analyses revealed that potent infiltration of CD8+ T cells into tumors with target antigen expression was observed in 12 of 20 (60%) patients. Conclusions: This novel therapeutic vaccine was safe as perioperative immunotherapy for patients with HCC, and has the potential to strongly induce CD8+ T cells infiltration into tumors.

Original languageEnglish
Pages (from-to)649-660
Number of pages12
JournalHepatology Research
Volume53
Issue number7
DOIs
Publication statusPublished - 2023 Jul
Externally publishedYes

Keywords

  • hLAG-3Ig plus poly-ICLC
  • hepatocellular carcinoma
  • peptide vaccination therapy
  • tumor immunogenicity

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Phase I study of a novel therapeutic vaccine as perioperative treatment for patients with surgically resectable hepatocellular carcinoma: The YCP02 trial'. Together they form a unique fingerprint.

Cite this