Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination An autopsy case

Yu Sawada, Toshiaki Yoshikawa, Satoshi Fujii, Shuichi Mitsunaga, Daisuke Nobuoka, Shoichi Mizuno, Mari Takahashi, Chisako Yamauchi, Itaru Endo, Tetsuya Nakatsura

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1228-1233
Number of pages6
JournalHuman Vaccines and Immunotherapeutics
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Fingerprint

Glypicans
Hepatocellular Carcinoma
Autopsy
Vaccination
Peptides
Neoplasms
Subunit Vaccines
Heart Atria
Cause of Death
Thrombosis
Necrosis
Clinical Trials, Phase I
Liver
Cytotoxic T-Lymphocytes
Clinical Protocols
Disease Progression
Shock
Fever
Vaccines
Clinical Trials

Keywords

  • CTL
  • Glypican-3
  • HCC
  • Peptide vaccine
  • Tumor necrosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination An autopsy case. / Sawada, Yu; Yoshikawa, Toshiaki; Fujii, Satoshi; Mitsunaga, Shuichi; Nobuoka, Daisuke; Mizuno, Shoichi; Takahashi, Mari; Yamauchi, Chisako; Endo, Itaru; Nakatsura, Tetsuya.

In: Human Vaccines and Immunotherapeutics, Vol. 9, No. 6, 06.2013, p. 1228-1233.

Research output: Contribution to journalArticle

Sawada, Y, Yoshikawa, T, Fujii, S, Mitsunaga, S, Nobuoka, D, Mizuno, S, Takahashi, M, Yamauchi, C, Endo, I & Nakatsura, T 2013, 'Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination An autopsy case', Human Vaccines and Immunotherapeutics, vol. 9, no. 6, pp. 1228-1233. https://doi.org/10.4161/hv.24179
Sawada, Yu ; Yoshikawa, Toshiaki ; Fujii, Satoshi ; Mitsunaga, Shuichi ; Nobuoka, Daisuke ; Mizuno, Shoichi ; Takahashi, Mari ; Yamauchi, Chisako ; Endo, Itaru ; Nakatsura, Tetsuya. / Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination An autopsy case. In: Human Vaccines and Immunotherapeutics. 2013 ; Vol. 9, No. 6. pp. 1228-1233.
@article{4da934040e1644478a3c3f7ee23b7c29,
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.",
keywords = "CTL, Glypican-3, HCC, Peptide vaccine, Tumor necrosis",
author = "Yu Sawada and Toshiaki Yoshikawa and Satoshi Fujii and Shuichi Mitsunaga and Daisuke Nobuoka and Shoichi Mizuno and Mari Takahashi and Chisako Yamauchi and Itaru Endo and Tetsuya Nakatsura",
year = "2013",
month = "6",
doi = "10.4161/hv.24179",
language = "English",
volume = "9",
pages = "1228--1233",
journal = "Human Vaccines and Immunotherapeutics",
issn = "2164-5515",
publisher = "Landes Bioscience",
number = "6",

}

TY - JOUR

T1 - Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination An autopsy case

AU - Sawada, Yu

AU - Yoshikawa, Toshiaki

AU - Fujii, Satoshi

AU - Mitsunaga, Shuichi

AU - Nobuoka, Daisuke

AU - Mizuno, Shoichi

AU - Takahashi, Mari

AU - Yamauchi, Chisako

AU - Endo, Itaru

AU - Nakatsura, Tetsuya

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

KW - CTL

KW - Glypican-3

KW - HCC

KW - Peptide vaccine

KW - Tumor necrosis

UR - http://www.scopus.com/inward/record.url?scp=84880688113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880688113&partnerID=8YFLogxK

U2 - 10.4161/hv.24179

DO - 10.4161/hv.24179

M3 - Article

VL - 9

SP - 1228

EP - 1233

JO - Human Vaccines and Immunotherapeutics

JF - Human Vaccines and Immunotherapeutics

SN - 2164-5515

IS - 6

ER -