Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bingjia He, MD; Phone Number: +862039195965; Email: 464677938@qq.com
• Study Contact Backup: Name: Zhenfeng Zhang, MD, PhD; Phone Number: +862039195966; Email: zhangzhf@gzhmu.edu.cn

Study Locations

• China
  • Guangzhou, China, 510260
    • Recruiting
    • Second Affiliated Hospital of Guangzhou Medical University
    • Contact: Bingjia He; Phone Number: +862039195965; Email: 464677938@qq.com
    • Contact: Zhenfeng Zhang, MD, PhD; Phone Number: +862039195966; Email: zhangzhf@gzhmu.edu.cn
    • Principal Investigator: Zhenfeng Zhang, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers	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.	15 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Collaborators: Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
• Investigators: Principal Investigator: Zhenfeng Zhang, MD, PhD, Second Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): January 1, 2035

Study Registration Dates

• First Submitted: April 4, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (Actual): April 13, 2021

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 22, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer; Solid Tumor; PD1; TIL; Mesothelin; GPC3; B7-H3; CTLA4; liver Cancer; CAR-TIL; CRISPRA-CAS9
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplasms; Liver Neoplasms
• Other Study ID Numbers: ZZTIL-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No