Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Liver Cancer; Lung Cancer; CTLA4; Colo-rectal Cancer; Solid Tumor, Adult; Breast Cancer; Brain Tumor; PD1
• Interventions: Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3

• Registration Number: NCT04842812
• Lead Sponsor: Second Affiliated Hospital of Guangzhou Medical University

Brief Summary

Tumor infiltration lymphocytes (TILs) have been harvested from advanced cancer patients and constructed to knockout PD1 gene and express scFvs against both PD1 and CTALA4 and CARs against various antigens, followed by transfusion into the patients. The safety, tolerance, and preliminary clinical efficacy of the TILs will be evaluated.

Detailed Description

1. Choose appropriate patients with advanced lung or other cancers, with written consent for this study;

2. Perform biopsy or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol;

3. Grow TILs and engineered the tumor-effective TILs with CRISPRA-CAS9 technique to knockdown PD1 and electronic-transfection strategy to express scFvs that target PD1 and CTLA4; amplify the engineered T cells as needed, test the quality and killing activity of the TILs and then transfuse them back the patients via systemic or local injections via standard protocol, and follow up closely to collect related parameters as needed;

4. To enhance the killing capability, tumor-noneffective TILs have also been genetically engineered to express various CARs targeting HER2/Mesothelin/Lewis-Y/PSCA/MUC1/ GPC3/AXL/EGFR/Claudin18.2/B7-H3/ROR1/GD2/AXL/Claudin6-DAP10 with knockdown of PD1/HPK1 as appropriate;

5. Evaluate the clinical results as needed.

Study Timeline

• Study Start: 2021-01-01
• Study First Submitted: 2021-04-04
• Study First Submitted QC: 2021-04-09
• Study First Posted: 2021-04-13
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-22
• Last Update Posted: 2024-06-25
• Primary Completion: 2029-12-31
• Study Completion: 2035-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Patients with advanced cancers that failed to current available therapies;
2. Life expectancy >12 weeks;
3. Adequate heart, lung, liver, kidney functions;
4. Available for tumor biopsy or cancerous effusions;
5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TILs/CAR-TILs treatment	TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3	Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment.

Primary Outcome Measures

Name	Time	Method
Safety of TILs/CAR-TILs treatment in advanced solid cancers	up to 36 months	Assessing Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

Secondary Outcome Measures

Name	Time	Method
Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers	15 years	Assessing various clinical response rates including complete response, partial response, stable disease, and progress disease during and after TILs/CAR-TILs treatment in advanced solid cancers.

Trial Locations

Locations (1)

Second Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, China