title: Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination: an autopsy case.
abstract: We recently reported the safety, immunological and clinical responses to a GPC3-derived peptide vaccine in a phase I clinical trial of patients with advanced hepatocellular carcinoma (HCC). We conducted a subsequent trial in advanced HCC to assess the histopathological findings before and after vaccination with the GPC3 peptide. Here, we present the clinical course and the pathological study including the autopsy of a patient with advanced HCC in the ongoing clinical trial. A 62-year old patient suffering from HCC refractory to sorafenib therapy received the GPC3 peptide vaccine. The patient had fever and remarkably impaired liver function twice after vaccination. Contrast-enhanced CT after the second vaccination showed multiple low-density areas in the liver tumor, indicating tumor necrosis. In contrast, the tumor thrombus in the right atrium increased. The patient discontinued protocol treatment due to disease progression and died 30 days after the second vaccination. An autopsy was performed to determine the main cause of death and to evaluate the antitumor effect of the vaccination. A histological examination showed central necrosis in most of the intrahepatic tumor. The main cause of death was circulatory failure due to tumor thrombus, which occupied most of the right atrium. An immunohistochemical analysis revealed infiltration of CD8-positive T cells in the residual carcinoma, but not within the cirrhotic area. Ex vivo IFN-γ enzyme-linked immunospot analysis revealed vaccine-induced immune-reactivity against the GPC3 peptide. A histopathological examination at the estimated time of a strong immunological response demonstrated a GPC3 peptide vaccination-induced cytotoxic T-lymphocyte response with an anti-tumor effect.
authors: Division of Cancer Immunotherapy; National Cancer Center Hospital East; Kashiwa, Chiba Japan; Department of Gastroenterology; Yokohama City University; Yokohama, Kanagawa Japan.
authors: Yu
authors: Y
authors: Sawada
authors: Toshiaki
authors: T
authors: Yoshikawa
authors: Satoshi
authors: S
authors: Fujii
authors: Shuichi
authors: S
authors: Mitsunaga
authors: Daisuke
authors: D
authors: Nobuoka
authors: Shoichi
authors: S
authors: Mizuno
authors: Mari
authors: M
authors: Takahashi
authors: Chisako
authors: C
authors: Yamauchi
authors: Itaru
authors: I
authors: Endo
authors: Tetsuya
authors: T
authors: Nakatsura
mesh_terms: D001344:Autopsy; D019496:Cancer Vaccines / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000556:secondary / Q000628:therapy*; D004699:Endocardium / Q000473:pathology; D053673:Glypicans / Q000008:administration & dosage*; D006338:Heart Neoplasms / Q000150:complications / Q000473:pathology* / Q000556:secondary; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms; D012769:Shock; D013927:Thrombosis
chemical_list: D019496:Cancer Vaccines; C105937:GPC3 protein, human; D053673:Glypicans
keywords: CTL; HCC; glypican-3; peptide vaccine; tumor necrosis