Pilot Study of NKG2D-Ligand Targeted CAR-NK Cells in Patients With Metastatic Solid Tumours

Study Overview
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Brief Summary
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This is a single-centre, single arm, open-label pilot study to evaluate the safety and feasibility of CAR-NK cell treatment in subjects with metastatic solid tumours. Autologous or allogeneic NK cells are transfected by mRNA electroporation to prepare investigational CAR-NK cells with transiently enhanced specificity and activity against NKG2D-ligand expressing cancer cells.

Official Title
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Pilot Study of NKG2D-Ligand Targeted CAR-NK Cells in Patients With Metastatic Solid Tumours

Conditions
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Solid Tumours

Intervention / Treatment
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* Biological: CAR-NK cells targeting NKG2D ligands


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form must be obtained prior to any research procedure. Histologically or cytologically confirmed diagnosis of metastatic solid tumours ECOG performance status of 0-3; Adequate organ function defined as: ANC≥1.0×10^9/L, PLT≥75×10^9/L, ALB≥25g/L, TBIL≤1.5×ULN, AST≤2.5×ULN, ALT≤2.5×ULN, ALP≤2.5×ULN, Cr≤1.5×ULN; The patient's own PBMCs or PBMCs from a biological parent or child who is willing to donate blood will be used to prepare CAR-NK cells. The parent or child should be ≥18 and ≤60 years old, and he or she is able to sign the informed consent for blood donation by himself/herself; Patients who won't benefit from surgery, or refuse surgical treatment; patients who won't benefit from chemotherapy, can't tolerate chemotherapy or refuse chemotherapy. Patients volunteer to participate in this study and sign the informed consent form for subjects; Blood donors sign the informed consent form for blood donors. Blood donors have negative test results for HIV, HBV and HCV; If a subject or blood donor is a female of childbearing potential, she must have a negative urine pregnancy test result. Exclusion Criteria: Patients who are suffering from uncontrollable or active infectious diseases of the hematological system, cardiovascular system, respiratory system, digestive system, urinary system, or the endocrine system; Patients with immunologic deficiency or autoimmune diseases; Patients with severe hypersensitivity reactions; Patients received other forms of cellular therapies within the last 3 months; Patients received systemic steroids within the last 3 months; Patients who are breastfeeding or pregnant; Patients with brain metastases; Patients who have received an organ transplant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-NK cells targeting NKG2D ligands<br> | Biological: CAR-NK cells targeting NKG2D ligands<br>* The infusion of CAR-NK cells will be performed in the Third Affiliated Hospital of Guangzhou Medical University. Following infusion of CAR-NK cells, interleukin-2 (IL-2) will be injected subcutaneously into some patients to support the in vivo survival of CAR-NK cells. The subject will be observed for any side effects during this time and all the adverse events will be recorded.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events |  | from day 0 - month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumour response due to CAR-NK cell infusions |  | 100 days after CAR-NK cell infusion |