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

BACKGROUND: 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-HLA-binding heat shock protein (HSP)70/glypican-3 (GPC3) 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 ten times after surgery to patients with untreated, surgically resectable HCC (stage II to IVa). The primary endpoints of this study were the safety and feasibility of this treatment. We also analyzed the resected tumor specimens pathologically using hematoxylin and eosin staining and immunohistochemistry for HSP70, GPC3, CD8 and PD-1.

RESULTS: Twenty HLA-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. This article is protected by copyright. All rights reserved.