Cellular based treatment modalities for unresectable hepatocellular carcinoma

Abstract

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.