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| Name | Class |
|---|---|
| Hunan Zhaotai Yongren Medical Innovation Co. Ltd. | OTHER |
| Guangdong Zhaotai InVivo Biomedicine Co. Ltd. | OTHER |
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The third generation of CAR-T cells that target GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR 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 GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR
-CAR-T cell immunotherapy on human cancers will firstly be tested.
Choose appropriate patients with advanced lung or other cancers,with written consent for this study;
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;
Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR 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;
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 GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR
-DAP10-CAR with knockdown of PD1/HPK1;
Other cancers with these cell surface antigen expressions are also recruited if needed;
Evaluate the clinical results as needed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAR-T cell therapy group | Experimental | Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR | Biological | CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients with Dose Limiting Toxicity | A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR T cells,which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5. | three months |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Patients with best response as either complete remission or partial remission. | 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. | three months |
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Inclusion Criteria:
1. Patients with advanced cancer that expresses GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR 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 ofGPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR-CAR determined by flow-cytometry and killing of GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR-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.
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Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhenfeng Zhang, MD,PhD | Contact | 0086-020-34153532 | zhangzhf@gzhmu.edu.cn | |
| Peng Li, PhD | Contact | +86 20 32015300 | lipeng@invivobio.com.cn |
| Name | Affiliation | Role |
|---|---|---|
| Zhenfeng Zhang, MD,PhD | Second Affiliated Hospital of Guangzhou Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Sun Yat-sen University | Recruiting | Guangzhou | Guangdong | 510072 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28405515 | Result | 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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Use engineered CAR-T cells to kill cancer cells with certain targets.
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|
| Median CAR-T cell persistence | Median CAR-T cell persistence will be measured by quantitative rt-PCR. | Six years |
| The Second Affiliated Hospital of Guangzhou Medical University | Recruiting | Guangzhou | Guangdong | 510260 | China |
|
| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D000090204 | Mesothelin |
| D006162 | Guanylate Cyclase |
| C110843 | PSCA protein, human |
| ID | Term |
|---|---|
| D058851 | GPI-Linked Proteins |
| D008562 | Membrane Glycoproteins |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D047908 | Intracellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D058635 | Lipid-Linked Proteins |
| D008565 | Membrane Proteins |
| D000954 | Antigens, Surface |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D019761 | Phosphorus-Oxygen Lyases |
| D008190 | Lyases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
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