Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy

Tan, Anthony T.; Yang, Ninghan; Krishnamoorthy, Thinesh Lee; Oei, Vincent Yi Sheng; Chua, Alicia; Zhao, Xinyuan; Tan, Hui Si; Chia, Adeline; Bert, Nina Le; Low, Diana; Tan, Han Khim; Kumar, Rajneesh; Irani, Farah Gillan; Ho, Zi Zong; Zhang, Qi; Guccione, Ernesto; Wai, Lu-En; Koh, Sarene; Hwang, William Ying Khee; Chow, Wan Cheng; Bertoletti, Antonio

doi:10.1053/j.gastro.2019.01.251

Cited by 108 publications

(123 citation statements)

References 43 publications

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“…10,11 A recent study by Tan et al demonstrated a proof of principle that T-cell therapy could be tailored to target antigens from integrated HBV as a personalized TCR T-cell immunotherapy for HBV-related HCC. 13 In this study, it was shown that HBV-related HCC tumor cells expressed antigenic epitopes translated from the short integrated HBV mRNAs, that could be detected by and resulting in T-cell activation. 13 Autologous T cells were engineered to express the selected TCRs specific for epitopes of HBV-DNA from metastases and were adoptively transferred to two HCC patients with recurrence after liver transplantation.…”

Section: Engineered T-cell Therapymentioning

confidence: 85%

“…13 In this study, it was shown that HBV-related HCC tumor cells expressed antigenic epitopes translated from the short integrated HBV mRNAs, that could be detected by and resulting in T-cell activation. 13 Autologous T cells were engineered to express the selected TCRs specific for epitopes of HBV-DNA from metastases and were adoptively transferred to two HCC patients with recurrence after liver transplantation. This personalized T-cell therapy is proven to be safe in both patients with one patient showing reduction in volume of metastases during the treatment.…”

Section: Engineered T-cell Therapymentioning

confidence: 85%

“…10,11 In fact, recent attempts to treat HBV-related HCC by targeting HBV antigen resulted in promising benefit. 12,13 On the other hand, HCV viral genomic RNA encodes for a polyprotein, which is processed by host and viral proteases into at least 10 different proteins. 14 There is currently no HCV vaccine available due to many challenges in vaccine development including high variability of HCV virus and the lack of suitable in vitro and in vivo models.…”

Section: Mutational Landscapes In Viral-related Hccsmentioning

confidence: 99%

“…This personalized T-cell therapy is proven to be safe in both patients with one patient showing reduction in volume of metastases during the treatment. 13 For chronic HCV infection, a CAR-T against HCV targeting the HCV/E2 glycoprotein was previously constructed to control HCV infection and it was capable of secreting antiviral and pro-inflammatory cytokines and lysing HCV-infected hepatocytes in vitro. 79 However, there is currently no clinical trial with such HCV-targeting CAR-T therapy and the efficacy in a clinical setting for HCV-related HCC remains to be tested.…”

Section: Engineered T-cell Therapymentioning

confidence: 99%

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Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma

Lim

Chew

2019

Semin Liver Dis

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Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20%), with mixed reports on response rates in hepatitis viral-related HCC as compared with nonviral HCC. Given such complexity in response to immunotherapy, it is increasingly appreciated that deeper understanding of the tumor molecular features and tumor microenvironment of hepatitis viral-related HCC is crucial for the design of more effective immunotherapeutics. We discuss herein the current knowledge in tumor genomic mutational and immune landscapes as well as the ongoing immunotherapy trials in HCC with the unique focus on their viral etiologies. Based on this understanding, we also outline perspectives and rationale on the design of potential immunotherapeutic strategies in HCC patients according to their viral etiologies.

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Section: Engineered T-cell Therapymentioning

confidence: 85%

Section: Engineered T-cell Therapymentioning

confidence: 85%

Section: Mutational Landscapes In Viral-related Hccsmentioning

confidence: 99%

Section: Engineered T-cell Therapymentioning

confidence: 99%

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Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma

Lim

Chew

2019

Semin Liver Dis

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“…Among these methods, sonoporation has shown potential to express pro-apoptotic genes in HCC cells in vitro [143] and deliver shRNA of frizzled-2 to suppress HCC in vitro [144]. Electroporation has been used for delivering TRAIL/Apo2L gene to induce apoptosis [145]; the IL-12 gene to induce immune responses to HCC [146,147]; more recently, to deliver mRNA into T-cells to develop specific T-cells for HCC immunotherapy [148]; and GPC-3 CAR-T-cells [149]. Magnetofection has also been used to deliver genes into HCC cell lines combined with ternary organic-inorganic hybrid nanocomposites containing deferoxamine-coated iron oxide nanoparticles, plasmid DNA, and branched polyethyleneimine [150].…”

Section: Non-viral Gene Delivery Using Physical Methodsmentioning

confidence: 99%

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

Kamimura

Yokoo

Abé

et al. 2019

Cancers

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The liver is a key organ for metabolism, protein synthesis, detoxification, and endocrine function, and among liver diseases, including hepatitis, cirrhosis, malignant tumors, and congenital disease, liver cancer is one of the leading causes of cancer-related deaths worldwide. Conventional therapeutic options such as embolization and chemotherapy are not effective against advanced-stage liver cancer; therefore, continuous efforts focus on the development of novel therapeutic options, including molecular targeted agents and gene therapy. In this review, we will summarize the progress toward the development of gene therapies for liver cancer, with an emphasis on recent clinical trials and preclinical studies.

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Designing the next‐generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures

et al. 2021

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In the mid-90s, hepatitis B virus (HBV)-directed immune responses were for the first time investigated in detail and revealed suboptimal T-cell responses in chronic HBV patients. Based on these studies, therapeutic vaccination exploiting the antigen presentation capacity of dendritic cells to prime and/or boost HBVspecific T-cell responses was considered highly promising. Now, 25 years later, it has not yet delivered this promise. In this review, we summarise what has been clinically tested in terms of antigen targets and vaccine forms, how the immunological and therapeutic effects of these vaccines were assessed and what major clinical and immunological findings were reported. We combine the lessons learned from these trials with the most recent insights on HBV antigen presentation, T-cell responses, vaccine composition, antiviral and immune-modulatory drugs and disease biomarkers to derive novel opportunities for the next generation of therapeutic vaccines designed to cure chronic HBV either alone or in combination therapy.

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Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy

Cited by 108 publications

References 43 publications

Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma

Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

Designing the next‐generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures

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