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

Phase 1

Recruiting

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

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

Brief Summary: 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)

Detailed 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.

Recruitment & Eligibility

Inclusion Criteria

patients with advanced ovarian cancer or other cancers with expression of claudin6.
Life expectancy >12 weeks
Adequate heart,lung,liver,kidney function
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
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
CAR-NK cell plus NAD therapy group	Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells	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.
CAR-NK cell plus CBD therapy group	Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells	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.
CAR-NK cell therapy group	Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells	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.
PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group	Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells	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.
IL7/CCL19 secreting CAR-NK cell therapy group	Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells	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.

Primary Outcome Measures

Name	Time	Method
Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0	After CAR-NK cells infusion, up to 52 weeks.	The type, frequency, severity, and duration of adverse events as a result of Claudin6, GPC3, Mesothelin, or AXL- CAR-NK cells infusion will be summarized.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	After CAR-NK cells infusion, up to 52 weeks.	Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response, prior to progression or further anti-cancer therapy.
Duration of response (DOR)	up to 36 months	Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1/recurrence) or death from any cause, whichever occurs first.
Disease control rate (DCR)	up to 52 weeks.	Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after the first dose) is observed as best overall response.

Locations (1): The Second Affiliated Hospital of Guangzhou Medical University
🇨🇳
Guangzhou, Guangdong, China