CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors

Second Affiliated Hospital of Guangzhou Medical University

Status and phase: Enrolling; Phase 1

Conditions: CAR NK; Stage IV Ovarian Cancer; Testis Cancer, Refractory; Endometrial Cancer Recurrent

Treatments: Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

Study type: Interventional

Funder types: Other

Identifiers

NCT05410717

ZZCARNK-017

Details and patient eligibility

About

This study is an open, exploratory clinical study to evaluate the safety and preliminary efficacy of Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in patients with Claudin6, GPC3, Mesothelin, or AXL-positive advanced solid tumors (ovarian cancer and others)

Full description

1. Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study;
2. Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6, GPC3, Mesothelin, or AXL targeting CAR, amplify the number of transfected NK cells as needed, test the quality and killing activity of the Claudin6, GPC3, Mesothelin, or AXL-CAR-NK cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
3. To enhance the killing capability, some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3; some CAR-NK cells are combined with Cannabidiol(CBD) or Nicotinamide adenine dinucleotide (NAD);
4. Evaluate the clinical results as needed.
5. Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. patients with advanced ovarian cancer or other cancers with expression of claudin6.
2. Life expectancy >12 weeks
3. Adequate heart,lung,liver,kidney function
4. Available autologous transduced NK cells with greater than or equal to 20% expression of Claudin6, GPC3, Mesothelin, or AXL-CAR determined by flow-cytometry and killing of claudin6-positive targets greater than or equal to 20% in cytotoxicity assay
5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion criteria

1. Had accepted gene therapy before;
2. Tumor size more than 25cm;
3. Severe virus infection such as HBV,HCV,HIV,et al
4. Known HIV positivity
5. History of liver/renal transplantation
6. Active infectious disease related to bacteria, virus,fungi,et al
7. Other severe diseases that the investigators consider not appropriate;
8. Pregnant or lactating women
9. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
10. Other conditions that the investigators consider not appropriate. -

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 5 patient groups

CAR-NK cell therapy group

Experimental group

Description:

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell therapy group.

Treatment:

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

IL7/CCL19 secreting CAR-NK cell therapy group

Experimental group

Description:

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the IL7/CCL19 secreting CAR-NK cell therapy group.

Treatment:

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group

Experimental group

Description:

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group.

Treatment:

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

CAR-NK cell plus CBD therapy group

Experimental group

Description:

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus CBD therapy group.

Treatment:

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

CAR-NK cell plus NAD therapy group

Experimental group

Description:

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus NAD therapy group.

Treatment:

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells