Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma

From preclinical studies to future perspectives

Yukai He, Sha Wu

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

AFP has been serving as a biomarker for the diagnosis of HCC for many years. Now, research has been conducted to use it as an immunological target for HCC immunotherapy. However, because of the self-nature of AFP, the immune activation and antitumor effects of the current AFP-based vaccines are weak. T cell epitope engineering was employed to create immunogenic AFP. A proof of principle was obtained in an animal model, demonstrating that the epitope-engineered-AFP gene vaccine indeed potently activated AFP-specific CD8 T cells, which critically could cross-recognize native-AFP peptides and kill AFP+ tumor cells. Importantly, immunization with engineered AFP increased liver infiltration of AFP-specific CD8 T cells and prevented the carcinogen-induced autochthonous HCC. In addition, prime-boost immunization with engineered AFP gene vaccine generated CD8 memory cells that could detect and respond to evolving HCC tumor cells, enhancing the prevention of autochthonous HCC. This study provides a blueprint for us to develop effective human AFP-based HCC vaccines that may be used to prevent HCC relapse after liver resection and de novo tumor development in high-risk populations. In addition, the new AFP-based HCC vaccines may allow us to identify high-quality TCR genes for engineering human T cells for adoptive immunotherapy of HCC as our effort.

Original languageEnglish (US)
Title of host publicationAlpha-Fetoprotein
Subtitle of host publicationFunctions and Clinical Applications
PublisherNova Science Publishers, Inc.
Pages375-391
Number of pages17
ISBN (Electronic)9781634849005
ISBN (Print)9781634848756
StatePublished - Jan 1 2016

Fingerprint

T-cells
alpha-Fetoproteins
Immunotherapy
Hepatocellular Carcinoma
Vaccines
T-Lymphocytes
Immunization
Tumors
Genes
Liver
Cells
Cell Engineering
Adoptive Immunotherapy
Blueprints
Neoplasms
T-Lymphocyte Epitopes
Human Engineering
Biomarkers
Human engineering
Infiltration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

He, Y., & Wu, S. (2016). Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma: From preclinical studies to future perspectives. In Alpha-Fetoprotein: Functions and Clinical Applications (pp. 375-391). Nova Science Publishers, Inc..

Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma : From preclinical studies to future perspectives. / He, Yukai; Wu, Sha.

Alpha-Fetoprotein: Functions and Clinical Applications. Nova Science Publishers, Inc., 2016. p. 375-391.

Research output: Chapter in Book/Report/Conference proceedingChapter

He, Y & Wu, S 2016, Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma: From preclinical studies to future perspectives. in Alpha-Fetoprotein: Functions and Clinical Applications. Nova Science Publishers, Inc., pp. 375-391.
He Y, Wu S. Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma: From preclinical studies to future perspectives. In Alpha-Fetoprotein: Functions and Clinical Applications. Nova Science Publishers, Inc. 2016. p. 375-391
He, Yukai ; Wu, Sha. / Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma : From preclinical studies to future perspectives. Alpha-Fetoprotein: Functions and Clinical Applications. Nova Science Publishers, Inc., 2016. pp. 375-391
@inbook{c2d8ad6d063e424ab4641a76ee37ba4f,
title = "Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma: From preclinical studies to future perspectives",
abstract = "AFP has been serving as a biomarker for the diagnosis of HCC for many years. Now, research has been conducted to use it as an immunological target for HCC immunotherapy. However, because of the self-nature of AFP, the immune activation and antitumor effects of the current AFP-based vaccines are weak. T cell epitope engineering was employed to create immunogenic AFP. A proof of principle was obtained in an animal model, demonstrating that the epitope-engineered-AFP gene vaccine indeed potently activated AFP-specific CD8 T cells, which critically could cross-recognize native-AFP peptides and kill AFP+ tumor cells. Importantly, immunization with engineered AFP increased liver infiltration of AFP-specific CD8 T cells and prevented the carcinogen-induced autochthonous HCC. In addition, prime-boost immunization with engineered AFP gene vaccine generated CD8 memory cells that could detect and respond to evolving HCC tumor cells, enhancing the prevention of autochthonous HCC. This study provides a blueprint for us to develop effective human AFP-based HCC vaccines that may be used to prevent HCC relapse after liver resection and de novo tumor development in high-risk populations. In addition, the new AFP-based HCC vaccines may allow us to identify high-quality TCR genes for engineering human T cells for adoptive immunotherapy of HCC as our effort.",
author = "Yukai He and Sha Wu",
year = "2016",
month = "1",
day = "1",
language = "English (US)",
isbn = "9781634848756",
pages = "375--391",
booktitle = "Alpha-Fetoprotein",
publisher = "Nova Science Publishers, Inc.",

}

TY - CHAP

T1 - Engineering alpha-fetoprotein to develop vaccines and T cell immunotherapies for hepatocellular carcinoma

T2 - From preclinical studies to future perspectives

AU - He, Yukai

AU - Wu, Sha

PY - 2016/1/1

Y1 - 2016/1/1

N2 - AFP has been serving as a biomarker for the diagnosis of HCC for many years. Now, research has been conducted to use it as an immunological target for HCC immunotherapy. However, because of the self-nature of AFP, the immune activation and antitumor effects of the current AFP-based vaccines are weak. T cell epitope engineering was employed to create immunogenic AFP. A proof of principle was obtained in an animal model, demonstrating that the epitope-engineered-AFP gene vaccine indeed potently activated AFP-specific CD8 T cells, which critically could cross-recognize native-AFP peptides and kill AFP+ tumor cells. Importantly, immunization with engineered AFP increased liver infiltration of AFP-specific CD8 T cells and prevented the carcinogen-induced autochthonous HCC. In addition, prime-boost immunization with engineered AFP gene vaccine generated CD8 memory cells that could detect and respond to evolving HCC tumor cells, enhancing the prevention of autochthonous HCC. This study provides a blueprint for us to develop effective human AFP-based HCC vaccines that may be used to prevent HCC relapse after liver resection and de novo tumor development in high-risk populations. In addition, the new AFP-based HCC vaccines may allow us to identify high-quality TCR genes for engineering human T cells for adoptive immunotherapy of HCC as our effort.

AB - AFP has been serving as a biomarker for the diagnosis of HCC for many years. Now, research has been conducted to use it as an immunological target for HCC immunotherapy. However, because of the self-nature of AFP, the immune activation and antitumor effects of the current AFP-based vaccines are weak. T cell epitope engineering was employed to create immunogenic AFP. A proof of principle was obtained in an animal model, demonstrating that the epitope-engineered-AFP gene vaccine indeed potently activated AFP-specific CD8 T cells, which critically could cross-recognize native-AFP peptides and kill AFP+ tumor cells. Importantly, immunization with engineered AFP increased liver infiltration of AFP-specific CD8 T cells and prevented the carcinogen-induced autochthonous HCC. In addition, prime-boost immunization with engineered AFP gene vaccine generated CD8 memory cells that could detect and respond to evolving HCC tumor cells, enhancing the prevention of autochthonous HCC. This study provides a blueprint for us to develop effective human AFP-based HCC vaccines that may be used to prevent HCC relapse after liver resection and de novo tumor development in high-risk populations. In addition, the new AFP-based HCC vaccines may allow us to identify high-quality TCR genes for engineering human T cells for adoptive immunotherapy of HCC as our effort.

UR - http://www.scopus.com/inward/record.url?scp=85021883513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021883513&partnerID=8YFLogxK

M3 - Chapter

SN - 9781634848756

SP - 375

EP - 391

BT - Alpha-Fetoprotein

PB - Nova Science Publishers, Inc.

ER -