Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. May 24, 2021; 12(5): 290-308
Published online May 24, 2021. doi: 10.5306/wjco.v12.i5.290
Cellular based treatment modalities for unresectable hepatocellular carcinoma
Konstantinos Damiris, Hamza Abbad, Nikolaos Pyrsopoulos
Konstantinos Damiris, Hamza Abbad, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
Nikolaos Pyrsopoulos, Department of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
Author contributions: Damiris K, Abbad H, and Pyrsopoulos N equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision/editing; all authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors do not have any conflicts of interest relevant to this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Nikolaos Pyrsopoulos, FAASLD, AGAF, FACG, MD, PhD, Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 South Orange Ave, Newark, NJ 07103, United States.
Received: March 12, 2021
Peer-review started: March 12, 2021
First decision: April 6, 2021
Revised: April 19, 2021
Accepted: April 28, 2021
Article in press: April 28, 2021
Published online: May 24, 2021

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality. Early and intermediate stages of HCC allow for treatment with surgical resection, ablation and even liver transplantation, however disease progression warrants conventional systemic therapy. For years treatment options were limited to molecular-targeting medications, of which sorafenib remains the standard of care. The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of HCC, but there is an urgent need for the development of further novel therapeutic treatments that prolong overall survival and minimize recurrence. Current investigation is focused on adoptive cell therapy including chimeric antigen receptor-T cells (CAR-T cells), T cell receptor (TCR) engineered T cells, dendritic cells, natural killer cells, and tumor infiltrating lymphocyte cells, which have shown remarkable success in the treatment of hematological and solid tumor malignancies. In this review we briefly introduce readers to the currently approved systemic treatment options and present clinical and experimental evidence of HCC immunotherapeutic treatments that will hopefully one day allow for revolutionary change in the treatment modalities used for unresectable HCC. We also provide an up-to-date compilation of ongoing clinical trials investigating CAR-T cells, TCR engineered T cells, cancer vaccines and oncolytic viruses, while discussing strategies that can help overcome commonly faced challenges when utilizing cellular based treatments.

Keywords: Hepatocellular carcinoma, Immunotherapy, Immune cells, Adoptive T cell therapy, Chimeric antigen receptor-T cell, Clinical trials

Core Tip: Over the recent years investigation for safe and effective treatments for unresectable hepatocellular carcinoma (HCC) has shifted focus from various chemotherapeutic agents to immune based therapy. Although far from being finalized, immune cell-based therapy has shown efficacy in a variety of clinical trials, indicating possible future utilization alone or in combination for the prevention and treatment of HCC.