Immune Checkpoint Therapy in Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma (HCC) and Immune Checkpoint Therapy

Liver cancer is the second leading cause of cancer-related deaths globally. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and can be caused by chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), alcohol abuse, and metabolic syndrome-related to diabetes and obesity. In developed countries, surveillance programs lead to early HCC diagnosis in 40-50% of patients, at a stage amenable to potentially curative treatments. Patients with intermediate-stage HCC are treated with locoregional therapies, whereas those with advanced-stage disease can benefit from systemic therapies.

Immune checkpoint inhibitor (ICI) therapy, particularly antibodies targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, has represented a major breakthrough in drug development for oncology in the past decade. Anti-PD-1 or anti-PD-L1 monotherapy has been approved for the treatment of more than 10 cancer types, with objective response rates (ORRs) of 15-20% and good safety profiles. ICI therapy is also an attractive approach for new drug development in hepatocellular carcinoma.

Application of Immune Checkpoint Therapy in HCC

Locoregional therapy, including ablation therapy, transarterial chemoembolization (TACE), internal or external radiation therapy, and hepatic arterial infusion chemotherapy, is widely used for HCC management. These treatment modalities may induce immunogenic cell death by releasing tumor antigens from dying cancer cells and eliciting damage-associated molecular patterns, such as calreticulin and ATP release and type I interferon response, to facilitate antitumor immunity. Combinations of ICIs and locoregional therapies may further augment antitumor immunity without overlapping toxicity preliminary data from single-arm studies support the feasibility of this approach. In addition, anti-PD-1/anti-PD-L1 based combination therapy is expected to revolutionize the landscape of systemic therapy for HCC. Prioritizing different combination regimens will depend on our understanding of the actual immunomodulatory mechanisms in the various combinations, the availability and validity of predictive biomarkers, and the optimal prevention and management of immune-related adverse events (irAEs).

Mechanistic interaction between antitumor immunity and irAEs induced by immune checkpoint inhibitor therapy. Fig.1 Mechanistic interaction between antitumor immunity and irAEs induced by immune checkpoint inhibitor therapy. (Cheng, 2020)

Services at Creative Biolabs

As a professional immune checkpoint-related service provider, Creative Biolabs has a comprehensive technology platform and an excellent expert team. With rich experience and hundreds of successful precedents, we are confident in providing a series of quality-assured customer services for immune checkpoint-based HCC therapy development, including but not limited to:

If you are interested in any of our services, please do not hesitate to contact us for more information.

Reference

  1. Cheng, A. L.; et al. Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma. J Hepatol. 2020, 72(2): 307-319.

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