Application of mRNA Vaccine in Liver Transplantation for Hepatocellular Carcinoma

Overview

The therapeutic options for HCC include hepatectomy, liver transplantation, local ablation therapy, transarterial chemoembolization (TACE), radiotherapy, and systemic therapy. However, as early-stage HCC often presents with no obvious symptoms or atypical clinical manifestations, over 80% of patients are diagnosed at an advanced stage, losing the opportunity for surgical resection and leaving liver transplantation as the only potentially curative option. Nevertheless, even after liver transplantation, the recurrence rate of HCC remains as high as 30-45%. In recent years, with the successive launch of novel targeted drugs and immune checkpoint inhibitors, Chinese patients with HCC have gained more treatment options for both disease management and recurrence prevention. However, given the heterogeneity of HCC, only a subset of patients benefit from these therapies. Hepatitis B virus (HBV) infection is the primary risk factor for HCC, accounting for at least 50% of global HCC cases. In regions with high HBV prevalence-such as East and Southeast Asia, as well as sub-Saharan Africa-the proportion is even higher. While HBV-related HCC can be prevented through vaccination against HBV infection, no specific precision therapy currently exists for patients already diagnosed with HBV-positive HCC. Given that nucleic acid vaccine technology demonstrates value not only in disease prevention but also in immunotherapy-particularly mRNA therapeutic vaccines-this approach holds promise. mRNA therapeutic vaccines represent a highly promising new modality for tumor treatment. They offer advantages such as excellent safety, long-term expression, and sustained antigen presentation. Additionally, they can mimic the natural infection process of viruses to activate the immune system, eliciting robust immune responses against tumors. Currently, no mRNA therapeutic vaccines targeting HBV-related antigens have been approved for marketing. This HBV mRNA injection is an mRNA therapeutic vaccine encoding HBV-related specific antigens. Its active ingredient consists of modified mRNA encoding HBV-related antigen proteins, formulated into an injectable preparation via lipid nanoparticle (LNP) encapsulation. Preclinical safety evaluations have demonstrated that this vaccine exhibits low toxicity and good tolerability. Building on these preliminary results, this study aims to further evaluate its potential.

Interventions

• Biological HBV mRNA vaccine
  HBV mRNA vaccine

Primary outcome measures

• Dose-limiting toxicities (DLTs) and their incidence rates [Time frame: During one year after initial treatment]
• Safety: Type, frequency, and severity of treatment-related adverse events as assessed by CTCAE V5.0 [Time frame: During one year after initial treatment]

Secondary outcome measures (4)

• Objective response rate (ORR) [Time frame: During one year after initial treatment]
• Disease control rate (DCR) [Time frame: During one year after initial treatment]
• 1-year survival rate [Time frame: During one year after initial treatment]
• Immunogenicity: The level of antigen-specific T cells [Time frame: During one year after initial treatment]

Eligibility criteria

Inclusion criteria

• Male or female patients aged ≥18 years;
• Patients with histologically, cytologically, or clinically diagnosed hepatocellular carcinoma (HCC);
• Patients who, based on the investigator's assessment, meet the indications for liver transplantation and have expressed willingness to undergo transplantation, with a need for bridge therapy or downstaging therapy during the transplant waiting period as evaluated by the investigator;
• Positive for hepatitis B surface antigen (HBsAg) in peripheral blood;
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2; (Additional inclusion criteria may be supplemented.)

Exclusion criteria

• History of other malignancies, except for adequately treated and non-recurrent within 5 years prior to screening basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or gastrointestinal mucosal carcinoma, which the investigator deems eligible for inclusion;
• History of or current hepatic encephalopathy; known central nervous system (CNS) metastases that are untreated or not effectively controlled by prior therapy;
• Clinically significant ascites requiring therapeutic intervention at present;
• Known clinically significant uncontrolled cardiac symptoms or diseases;
• Any active autoimmune disease or history of autoimmune diseases, including but not limited to: neurologic diseases related to immunity, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disorders, scleroderma, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome (excluding type 1 diabetes mellitus controlled with stable-dose insulin); (Additional exclusion criteria may be supplemented.)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• West China Hospital, Sichuan University — Chengdu

Identifiers

NCT: NCT07077356 · HBV mRNA-Liver Tx

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗