This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 and CTLA-4 nanobodies (αPD1/CTLA-4-MSLN-CAR T cells) in patients with solid tumors.
Patients must have a histological or cytological diagnosis of advanced solid tumors, such as non-small-cell lung cancer and mesothelioma；
Patients must have failed established standard medical anti-cancer therapies；
Greater than or equal to 18 years of age and less than or equal to 70 years of age on day of signing informed consent；
Life expectancy ≥3 months；
Prior therapy with targeted therapy or cell therapy against MSLN；
Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell therapy home and abroad；
Active bacteria, viral or fungal infection, and not contained after anti-infective therapy (positive results in the blood ≤72 hours before infusion);
Patient is positive for Syphilis, Human Immunodeficiency Virus (HIV) , active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected);
Single group
αPD1/CTLA4-MSLN-CAR T cells
Biological/VaccineBZE2209 is prepared by non-viral vector technology consisting of autologous CD3+T cells expressing mesothelin-specific chimeric antigen receptor (CAR), PD1 nanoantibody and CTLA4 antibody with dimethyl sulfoxide as medium. It can be used for direct intravenous infusion. Autologous CD3+ T cells were transfected with plasmids expressing anti-mesothelin-specific CAR, anti-PD1 nanoantibody and anti-CTLA-4 antibody by electroporation in vitro. Mesothelin-specific CAR is a single-domain antibody (VHH) derived from alpaca, which is composed of a binding domain and a CD28 and CD3ζ chain signal transduction domain.
Dose-limiting toxicity（DLT）
Safety
Maximum tolerated dose (MTD)
Tolerability
Objective response rate (ORR)
Clinical response will be assessed by RECIST 1.1.
Progression-free survival (PFS)
PFS of patients receiving αPD1/CTLA4-MSLN-CAR T cells
Peak Plasma Concentration (Cmax)
Pharmacokinetics (PK)
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