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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • 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..