Safety and Efficacy of Metabolically Armed GPC3 CAR-T Cells Injection (Meta10-GPC3) in Patients With Unresectable Recurrent/Metastatic Hepatocellular Carcinoma

Exclusion Criteria

• •Pregnant or breastfeeding women, or women of childbearing potential who test positive on a pregnancy test during the screening period).
• •Active hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection; seropositivity for Human Immunodeficiency (HIV) or syphilis.
• •Any uncontrolled active infection, including but not limited to active pulmonary tuberculosis.
• •Therapeutic doses of corticosteroids must be discontinued at least 2 weeks prior to Meta10-GPC3 infusion; any immunosuppressive medications must be discontinued at least 4 weeks before signing the informed consent form.
• •History of hypersensitivity to immunotherapy or related agents, β-lactam antibiotics, or other severe allergic reactions.
• •History or presence of hepatic encephalopathy.
• •Clinically significant ascites, defined as ascites detectable on physical examination or requiring therapeutic intervention (excluding ascites detected only by imaging that does not require intervention).
• •Imaging showing that HCC occupies ≥ 50 % of normal liver volume, or presence of tumor thrombus in the main portal vein or inferior vena cava.
• •Clinically significant central-nervous-system (CNS) disorders (excluding subjects with CNS HCC metastases).
• •Active or decompensated cardiac illness (requiring hospitalization or surgical intervention within the past 6 months), or poorly pression ≥ 160/100 mmHg uncontrolled with medication. Stable coronary artery disease or well-controlled hypertension is allowed.
• •Active autoimmune disease requiring immunosuppressive therapy.
• •Prior organ transplantation or currently on an organ transplant waiting list (including but not limited to liver transplantation).
• •Any anti-HCC therapy within 2 weeks prior to leukapheresis or blood collection, including but not limited to surgical resection, interventional therapy, radiotherapy, chemotherapy, or immunotherapy.
• •History or concurrent presence of other malignancies, except for the following: surgically removed non-melanoma skin cancer, cured cervical carcinoma in situ, localized prostate cancer, low-stage bladder cancer, ductal carcinoma in situ of the breast, or any malignancy without recurrence or treatment within the past 2 years.
• •Other severe medical conditions, including but not limit to: poorly controlled diabetes (post-treatment HbA1c \> 7 %), severe cardiac dysfunction (LVEF \< 45 %), myocardial infarction, unstable angina, or unstable arrhythmia within 6 months, pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease, forced expiratory volume in 1 second (FEV1) \< 60 %, gastric ulcer, history of gastrointestinal bleeding, documented bleeding diathesis, uncontrolled thrombotic events, major bleeding, or DVT within 12 months prior to informed consent.
• •Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis).
• •History of QT-interval prolongation or severe cardiac disease.
• •Any other condition deemed by the investigator to make the subject unsuitable for participation in the study (e.g., poor compliance).