Allogeneic "Gammadelta T Cells (γδ T Cells)" Cell Immunotherapy in Phase 1 Hepatocellular Carcinoma Clinical Trial

The Safety Assessment of Ex-Vivo Expanded Allogeneic γδT Cells in Hepatocellular Carcinoma Patients in Phase 1 Clinical Trial

This study aims to evaluate the safety, tolerability and efficacy of ex-vivo expanded allogeneic γδT cells obtained from a blood-related donor of hepatocellular carcinoma patients.

This study is a single-center, non-randomized, open label, no control, prospective clinical trial to evaluate the safety, tolerability and efficacy of ex-vivo expanded allogeneic γδT cells from of a blood-related donor of Hepatocellular Carcinoma (HCC) Patients. This study will include the following sequential phases: sign informed consent, γδT cell pre-culture, screening and registration to the trial, apheresis, γδT cell preparation, treatments and follow-ups.

Patient Inclusion Criteria:

1. Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study.
2. Age 18 years up to the age of 65 (≤65), gender unlimited.
3. Hepatocellular Carcinoma diagnosed according to the 2018 edition of the EASL guidelines. Patients should accept liver biopsy voluntarily and histopathologically diagnosed with HCC.
4. Interventional therapy (e.g. TACE), RFA or radiation therapy should be at least 2 weeks prior to γδT cell transfusion; surgical treatment should be at least 1 month prior to γδT cell transfusion. Patients can take the first- or second-line targeted drugs recommended by the guidelines, such as lenvatinib or sorafenib.
5. Liver function: Child-Pugh class A/B (5-9)
6. Eastern Cooperative Oncology Group (ECOG) Performance score≤2.
7. Life expectancy of at least 1 year.
8. Patients combined with HBV infection require antiviral treatment with nucleoside analogues; patients combined with HCV infection require direct-acting antiviral agent (DAA) treatment.
9. Male and female patients of reproductive potential must agree to use birth control during the study and for at least 30 days post study.

Patient Exclusion Criteria:

1. Patients combined with HAV, HEV, HIV or other infectious diseases.

2. Acute infections, gastrointestinal bleeding, etc. occurred within 30 days before screening.

3. Women who are pregnant (urine/blood pregnancy test positive) or lactating; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.

4. Major organs dysfunction:

   • Peripheral blood: WBC<1.0×109/L, PLT <60×109/L, Hb <86g/L;
   • Coagulation: INR>2.3, PT>18s;
   • Liver function: ALB<28g/L, TBIL>51mmol/L, ALT/AST>5 times the upper limit of normal, CREA>1.5 times the upper limit of normal.

5. Combined with other severe organic diseases or mental illnesses, including any uncontrolled clinically significant systematic diseases such as urinary, circulatory, respiratory, neurological, psychiatric, digestive, endocrine and immune diseases.

6. Allergic constitution, history of allergies to blood products, known to be allergic to test substances.

7. Immunosuppressive or systemic cytotoxic drugs may require within 6 months prior to screening or during the study; 6 months prior to screening accepted other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.; immunotherapy such as PD-1 and PD-L1 antibodies.

8. Patients currently participating in other clinical trials who may violate this treatment plan and observations.

9. Those who are unable or unwilling to provide informed consent or who are unable to comply with the research requirements.

10. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed: patients with any serious acute or chronic physical or mental illness, or laboratory abnormalities.

Donor Inclusion Criteria:

1. Sign informed consent form.
2. Age 18 years up to the age of 50 (≤50), gender unlimited.
3. Relative to patients (unrestricted to blood relationship).
4. Apheresis available.
5. PLT≥100×109/L with normal APTT or PT.

Donor Exclusion Criteria:

1. History of any severe clinical diseases or other severe organic diseases, including any history of clinically significant systematic diseases such as cardiovascular, urinary, circulatory, respiratory, neurological, psychiatric, digestive and endocrine diseases. History of high blood pressure or systolic pressure>140 mmHg, diastolic pressure>90 mmHg in screening stage. Any situation that investigators believe is clinically significant or with other severe diseases unsuitable of apheresis.
2. Arterial thrombosis or venous thrombosis history 12 months prior to the trial or hemorrhagic tendency or history 2 months prior to the trial; oral administration of anticoagulation drugs (e. g. aspirin and warfarin).
3. Active or history of autoimmune diseases including but not restricted to SLE, psoriasis, RA, IBD and HT. Apart from hypothyrosis which can be controlled by hormone replacement therapy, skin diseases without systemic therapy and celiac disease which is fully controlled.
4. HIV-Ab, TP-Ab, HCV-Ab, HBsAg, HBeAg, HBeAb or HBcAb positive.
5. Any symptom, sign or laboratory examination abnormality suggesting acute or subacute infection (e.g. fever, cough, urinary irritation, skin infectious wound).
6. Female who are pregnant or cannot stop lactating.
7. Those who cannot communicate with medical staff due to mental illness or language disabilities.
8. Other unsuitable conditions that investigators believe unsuitable for the donation.