Clinical trial NCT04842812: Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Liver Cancer
Lung Cancer
Breast Cancer
Colo-rectal Cancer
Brain Tumor
Solid Tumor, Adult
PD1
CTLA4
Keywords: liver Cancer
Lung Cancer
Solid Tumor
TIL
CAR-TIL
PD1
CTLA4
GPC3
Mesothelin
B7-H3
CRISPRA-CAS9
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
First posted: 2021-04-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: TILs treatment of solid cancers
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Safety of TILs/CAR-TILs treatment in advanced solid cancers
timeFrame: up to 36 months
Secondary outcomes:
measure: Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers
timeFrame: 15 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Second Affiliated Hospital of Guangzhou Medical University
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Zhenfeng Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: