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

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.

Study Overview

• Status: Unknown
• Conditions: Solid Tumours
• Intervention / Treatment: Biological: CAR-NK cells targeting NKG2D ligands

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510150
      • Recruiting
      • Third Affiliated Hospital of Guangzhou Medical University
      • Contact: Lin Xiao, PhD; Phone Number: +86 15871810198; Email: linxiao120825@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent form must be obtained prior to any research procedure.
2. Histologically or cytologically confirmed diagnosis of metastatic solid tumours
3. ECOG performance status of 0-3;
4. 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;
5. 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;
6. 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.
7. Patients volunteer to participate in this study and sign the informed consent form for subjects;
8. Blood donors sign the informed consent form for blood donors.
9. Blood donors have negative test results for HIV, HBV and HCV;
10. If a subject or blood donor is a female of childbearing potential, she must have a negative urine pregnancy test result.

Exclusion Criteria:

1. 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;
2. Patients with immunologic deficiency or autoimmune diseases;
3. Patients with severe hypersensitivity reactions;
4. Patients received other forms of cellular therapies within the last 3 months;
5. Patients received systemic steroids within the last 3 months;
6. Patients who are breastfeeding or pregnant;
7. Patients with brain metastases;
8. Patients who have received an organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: CAR-NK cells targeting NKG2D ligands

Biological: CAR-NK cells targeting NKG2D ligands; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The Third Affiliated Hospital of Guangzhou Medical University
• Investigators: Principal Investigator: Xuehu Xu, MD, The Third Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• Ng YY, Du Z, Zhang X, Chng WJ, Wang S. CXCR4 and anti-BCMA CAR co-modified natural killer cells suppress multiple myeloma progression in a xenograft mouse model. Cancer Gene Ther. 2022 May;29(5):475-483. doi: 10.1038/s41417-021-00365-x. Epub 2021 Sep 1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 2, 2018
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (ACTUAL): January 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 1, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NRC-NK-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No