Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors

Sponsor

Second Affiliated Hospital of Guangzhou Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04842812

Collaborator

Guangdong Zhaotai InVivo Biomedicine Co. Ltd. (Other)

Enrollment

Location

Arm

168

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Cancer Lung Cancer Breast Cancer Colo-rectal Cancer Brain Tumor Solid Tumor, Adult PD1 CTLA4	Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3	Phase 1

Detailed Description

Choose appropriate patients with advanced lung or other cancers, with written consent for this study;
Perform biopsy or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol;
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;
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;
Evaluate the clinical results as needed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

TILs treatment of solid cancersTILs treatment of solid cancers

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Engineered TILs/CAR-TILs With PD1 Knockout and Anti-PD1/CTLA4-scFv Secreting or CARs Against Various Antigens to Treat Advanced Solid Tumors

Actual Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Jan 1, 2035

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TILs/CAR-TILs treatment Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment.	Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3 TILs and CAR-TILs injection: 1-10×10e7/kg cells for each treatment; 3 or more cycles.

Arm

Intervention/Treatment

Experimental: TILs/CAR-TILs treatment

Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment.

Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3

TILs and CAR-TILs injection: 1-10×10e7/kg cells for each treatment; 3 or more cycles.

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with advanced cancers that failed to current available therapies;
Life expectancy >12 weeks;
Adequate heart, lung, liver, kidney functions;
Available for tumor biopsy or cancerous effusions;
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;
Severe virus infection such as HBV, HCV, HIV, et al; Known HIV positivity;
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.