The third generation of CAR-T cells that target HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, or B7-H3 have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, or B7-H3 expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the HER2/Mesothelin/Lewis-Y/PSCA/MUC1/GPC3/AXL/EGFR/B7-H3 -CAR-T cell immunotherapy on human cancers will firstly be tested.
Full Title of Study: “CAR-T Cells Targeting HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, B7-H3 or Claudin18.2 for Immunotherapy of Lung Cancer: Phase I Clinical Trial”
- Study Type: Interventional
- Study Design
- Allocation: N/A
- Intervention Model: Single Group Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: August 1, 2022
1. Choose appropriate patients with advanced lung or other cancers,with written consent for this study; 2. Perform biopsy to determine the expression of HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 of the tumor by western blotting or IHC; 3. Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed; 4. To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express HER2/Mesothelin/Lewis-Y/PSCA/MUC1/ GPC3/AXL/EGFR/Claudin18.2/B7-H3-DAP10-CAR with knockdown of PD1/HPK1; 5. Other cancers with these cell surface antigen expressions are also recruited if needed; 6. Evaluate the clinical results as needed.
- Biological: CAR-T cells targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2, or B7-H3
- CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.
Arms, Groups and Cohorts
- Experimental: CAR-T cell therapy group
- Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.
Clinical Trial Outcome Measures
- Number of Patients with Dose Limiting Toxicity
- Time Frame: three months
- A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the PSCA/MUC1/GPC3/AXL/EGFR/B7-H3 -CAR T cells,which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
- Percent of Patients with best response as either complete remission or partial remission.
- Time Frame: three months
- Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.
- Median CAR-T cell persistence
- Time Frame: Six years
- Median CAR-T cell persistence will be measured by quantitative rt-PCR.
Participating in This Clinical Trial
1. Patients with advanced cancer that expresses PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 protein; 2. Life expectancy >12 weeks; 3. Adequate heart,lung,liver,kidney function; 4. Available autologous transduced T cells with greater than or equal to 20% expression of PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 CAR determined by flow-cytometry and killing of PSCA,MUC1,GPC3, AXL, EGFR, or B7-H3 -positive targets greater than or equal to 20% in cytotoxicity assay; 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; 3. Known HIV positivity; 4. Active infectious disease related to bacteria, virus,fungi,et al; 5. Other severe diseases that the investigators consider not appropriate; 6. Pregnant or lactating women; 7. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day); 8. Other conditions that the investigators consider not appropriate. -
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 75 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Second Affiliated Hospital of Guangzhou Medical University
- Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
- Provider of Information About this Clinical Study
- Overall Official(s)
- Zhenfeng Zhang, MD,PhD, Principal Investigator, Second Affiliated Hospital of Guangzhou Medical University
- Overall Contact(s)
- Zhenfeng Zhang, MD,PhD, 0086-020-34153532, firstname.lastname@example.org
Citations Reporting on Results
Wei X, Lai Y, Li J, Qin L, Xu Y, Zhao R, Li B, Lin S, Wang S, Wu Q, Liang Q, Peng M, Yu F, Li Y, Zhang X, Wu Y, Liu P, Pei D, Yao Y, Li P. PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells. Oncoimmunology. 2017 Feb 6;6(3):e1284722. doi: 10.1080/2162402X.2017.1284722. eCollection 2017.
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