Multi-Target Hi-TCR-T for Hepatocellular Carcinoma

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Registration Number	Trial Location	Study Design	Intervention
ChiCTR2500100163	Shanghai, China	Single arm	Intravenous infusion of 3.0×106 cells/kg of Super Hi-TCR-T cells targeting Nectin4, NKG2DL, TROP2, B7H3, GPC3, and FAP.

Ages 18-75

All Genders

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide, typically developing on the basis of long-term liver inflammation or cirrhosis. Major risk factors include hepatitis B (HBV), hepatitis C (HCV), chronic alcohol consumption, non-alcoholic steatohepatitis (NASH), aflatoxin exposure, and metabolic syndrome.

Despite continuous progress in surgical techniques, locoregional therapies, molecular targeted drugs, and immune checkpoint inhibitors, the overall prognosis for patients with advanced or recurrent hepatocellular carcinoma (HCC) remains unsatisfactory. The emergence of treatment resistance and significant biological heterogeneity of tumors remain key factors limiting the efficacy of existing treatments. Traditional TCR-T cell therapy relies on human leukocyte antigen (HLA) presentation of tumor antigens, and its clinical application is significantly limited by HLA matching requirements, resulting in a limited range of treatable patients. Therefore, new treatment strategies are urgently needed to overcome resistance and improve patient clinical outcomes.

Multi-Target Hi-TCR-T is a new generation T-cell immunotherapy strategy designed specifically for solid tumors, aiming to systematically address key challenges in HCC treatment. Hi-TCR-T cells are genetically engineered to recognize tumor-associated targets in an HLA-independent manner, significantly broadening the potential beneficiary population. Its multi-target design aims to address tumor heterogeneity by simultaneously targeting multiple tumor cells and tumor microenvironment-related antigens, reducing the risk of antigen escape and potentially decreasing disease recurrence.

This clinical trial is now open for recruitment of international patients, initiating an innovative treatment study for advanced hepatocellular carcinoma (HCC) that is unresectable and unsuitable for local therapy.

Treatment Protocol

This is an interventional study in the exploratory Phase I/II, designed as a single-arm clinical trial. All enrolled participants will receive Hi-TCR-T cell therapy, a next-generation engineered T cell treatment specifically designed for advanced or unresectable hepatocellular carcinoma (HCC). The therapy involves a single or multiple intravenous infusions at a dose of 3.0 × 10⁶ cells/kg.

Intervention Overview

The Hi-TCR-T cells are engineered to recognize and attack multiple tumor-associated antigens, including Nectin4, NKG2DL, TROP2, B7-H3, GPC3, and FAP. This multi-target design enhances tumor recognition and reduces the likelihood of tumor immune escape, providing a more comprehensive anti-tumor effect. The cells are further optimized with multiple functional enhancements.

Secreting IL-7 and super IL-15, which support T cell proliferation and persistence, enabling continuous recognition and killing of tumor cells.
Secreting CCL21, a chemokine that attracts additional immune cells to the tumor microenvironment, enhancing a coordinated anti-tumor immune response.
The cells express anti-TGFβ1 scFv and anti-PD-1 scFv, which block inhibitory signals in the tumor microenvironment, restore immune function, and boost T cell-mediated tumor killing.

More about Hi-TCR-T Cell Therapy

Treatment Process

Screening and Assessment: Comprehensive screening and baseline assessment, including histological or clinical confirmation of HCC, laboratory tests, and imaging studies, to ensure eligibility.
Standardized Hi-TCR-T Cell Infusion: Intravenous infusion of multi-target Hi-TCR-T cells (Nectin4, NKG2DL, TROP2, B7-H3, GPC3, FAP) at 3.0 × 10⁶ cells/kg.
Safety & Immune Monitoring: Predefined lab tests and imaging studies to monitor immune response and adverse events.
Follow-up Monitoring: Consistent follow-up schedule to assess tumor response, immune activation, and long-term safety.

Patient Recruitment Criteria

Inclusion Criteria

18-75 years (inclusive), regardless of gender.
Patients with advanced HCC who are inoperable and unsuitable for local therapy, and whose disease has progressed or cannot tolerate therapy after first - or second-line therapy, and who meet one of the following requirements:
- Histological or cytological diagnosis of HCC.
- According to authoritative guidelines or internationally recognized standards, the clinical diagnosis was HCC.
At least one measurable lesion was present according to RECIST1.1 and mRECIST criteria.
The expressions of Nectin4, NKG2DL, TROP2, B7H3 and GPC3 in tumor tissues were detected by immunohistochemistry in primary and metastatic specimens or in white paraffin sections of previous pathological pathology (the expression of tumor cells with a target >10% is considered positive, and at least 2 targets are required to be positive), as well as the expression of FAP in tumor tissues.
The patient's T cell quality (pre-experimental) assessment met the criteria: at least 5 times T cell proliferation within 3 days, and at least 10% lentivirus transduction efficiency.
ECOG performance status score of 0-2.
Child-Pugh score ≤6.
Expected survival time of at least 3 months.
No contraindications to peripheral blood mononuclear cell (PBMC) collection.

Seven days prior to the first treatment with the study drug, organ function levels must meet the following requirements:

Medical Testing	Parameter	Threshold / Criteria
Hematology	Hemoglobin (Hb)	≥90 g/L
	Absolute neutrophil count (ANC)	≥1.5×10⁹ /L
	Platelet count	≥75×10⁹ /L
Blood Biochemistry	Serum albumin	≥ 28 g/L
	Total bilirubin	≤ 2 × ULN
	AST (Aspartate aminotransferase)	≤ 3 × ULN
	ALT (Alanine aminotransferase)	≤ 3 × ULN
	Alkaline phosphatase (ALP)	≤ 3 × ULN
	Creatinine	≤ 1.5 × ULN
Coagulation	International standardized ratio (INR) or prothrombin time (PT)	≤1.5×ULN
Coagulation	Activated partial thromboplastin time (APTT)	≤1.5×ULN
Cardiac	Left ventricular ejection fraction (LVEF)	≥50% (Echocardiography confirms normal diastolic function. No serious arrhythmias)
Pulmonary and Renal Function	Blood oxygen saturation (room air)	≥92% (No serious lung or kidney disease. No active pulmonary infection.)

Serum pregnancy test results of women of childbearing age must be negative within 7 days before the first use of the study drug. Fertile men or women with the possibility of becoming pregnant must use a highly effective contraceptive method (such as oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicides) throughout the trial and continue contraception for 12 months after the end of treatment.
The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria

Treatment Cost

This clinical study is a chargeable treatment program. Participating patients are responsible for the costs of the study intervention and related examinations. The costs mainly include:

Cost of Hi-TCR-T cell preparation and injection treatment;
Cost of necessary blood, imaging, and other laboratory tests during treatment;
Fees for basic medical services during hospitalization (such as nursing care, medication, etc.).

For detailed fees, travel/visa support, accommodation and logistics, please contact us for a personalized consultation.

If you would like to learn more about this clinical trial, please feel free to reach out. We are here to provide a detailed introduction and arrange a private online consultation for you with the physician investigator.

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