Neoantigen Specific T Cells Derived From T Cell-Derived Induced Pluripotent Stem Cells for the Treatment of Hepatocellular Carcinoma: Potential and Challenges.

Fei Lu,Xun Li,Xiao-Jing-Nan Ma,Wei-Lin Jin,Yang Luo

doi:10.3389/fimmu.2021.690565

Fei Lu, Xun Li + Show 3 more

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https://doi.org/10.3389/fimmu.2021.690565

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Abstract

Immunotherapy has become an indispensable part of the comprehensive treatment of hepatocellular carcinoma (HCC). Immunotherapy has proven effective in patients with early HCC, advanced HCC, or HCC recurrence after liver transplantation. Clinically, the most commonly used immunotherapy is immune checkpoint inhibition using monoclonal antibodies, such as CTLA-4 and PD-1. However, it cannot fundamentally solve the problems of a weakened immune system and inactivation of immune cells involved in killing tumor cells. T cells can express tumor antigen-recognizing T cell receptors (TCRs) or chimeric antigen receptors (CARs) on the cell surface through gene editing to improve the specificity and responsiveness of immune cells. According to previous studies, TCR-T cell therapy is significantly better than CAR-T cell therapy in the treatment of solid tumors and is one of the most promising immune cell therapies for solid tumors so far. However, its application in the treatment of HCC is still being researched. Technological advancements in induction and redifferentiation of induced pluripotent stem cells (iPSCs) allow us to use T cells to induce T cell-derived iPSCs (T-iPSCs) and then differentiate them into TCR-T cells. This has allowed a convenient strategy to study HCC models and explore optimal treatment strategies. This review gives an overview of the major advances in the development of protocols to generate neoantigen-specific TCR-T cells from T-iPSCs. We will also discuss their potential and challenges in the treatment of HCC.

Highlights

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer worldwide and the third leading cause of cancer-related death, with approximately 50% of hepatocellular carcinoma (HCC) cases occurring in China [1]
Hafezi et al showed that HBV-specific T cell receptors (TCRs)-T cells have potential applications in organ transplantation patients with recurring HBV-HCC [20]. These results indicate that TCR-T cell therapy is efficient in the treatment of solid tumors such as HCC, and adoptive cell transfer therapy of liver cancer might eventually become the optimal solution in its comprehensive treatment
The application of T-induced pluripotent stem cells (iPSCs) to iPSCs for Hepatocellular Carcinoma Treatment generate a large number of tumor antigen-specific T cells solves the problem of short lifespan of activated cytotoxic T lymphocytes (CTLs) in traditional tumor immunotherapy

Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer worldwide and the third leading cause of cancer-related death, with approximately 50% of HCC cases occurring in China [1]. T cells express TCRs or CARs that recognize tumor antigens on the cell surface through gene editing technology, rendering T cells the specificity in their functions. IMPORTANCE OF NEOANTIGEN SPECIFIC T CELLS DERIVED FROM T-iPSCs in the Treatment of HCC

Results

Conclusion