Lung Cancer Cancer Immunotherapy CAR-T Cell

Biological: CAR-T cells targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, or CD80/86

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, or PD-L1 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, PD-L1, or CD80/86 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.     Evaluate the clinical results as needed.

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Brief Summary:

The third generation of CAR-T cells that target HER2, Mesothelin, Lewis-Y, PSCA, MUC1, PD-L1, or CD80/86 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, PD-L1 expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the HER2/Mesothelin/Lewis-Y/PSCA/MUC1/PD-L1/CD80/86-CAR-T cell immunotherapy on human cancers will firstly be tested.

Arms and Interventions

Arms

Experimental: CAR-T cell therapy group

Patients will receive 3 or more cycles of the CAR-T cells treatment via intra-tumor injection or vein, from 1x10e6/kg-10x10e6/kg weight.

Interventions

Biological: CAR-T cells targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, or CD80/86

CAR-T cells injection or transfusion: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.

Other Name: Administration of CAR-T cells through interventional technique.

Outcome Measures

Primary Outcome Measures

1.     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/PD-L1/CD80/86-CAR T cells,which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.

Secondary Outcome Measures

1.     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.

2.     Median CAR-T cell persistence [ Time Frame: Six years ]

Median CAR-T cell persistence will be measured by quantitative rt-PCR

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Criteria

Inclusion Criteria:

1. Patients with advanced cancer that expresses PSCA, MUC1, PD-L1, and/or CD80/86 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, PD-L1, or CD80/86 CAR determined by flow-cytometry and killing of PSCA,MUC1,PD-L1,or CD80/86-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.

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. -