This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to target mesothelin and express PD-1 antibodies in adult patients with advanced recurrent or refractory malignant solid tumors, which were positive expression of mesothelin.
This study will be conducted using a phase I/II trial design to assess the safety and efficacy of the PD-1 antibody expressing mesoCAR-T for patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors. MesoCAR-T can specifically and effectively kill the mesothelin positive cancer cells, PD-1 antibody are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors. The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells (PBMC) by leukapheresis, and then activated and engineered to express chimeric antigen receptors (CARs) targeting mesothelin and PD-1 antibody. Cells are proliferated in culture and returned to the patients by venous transfusion therapy. A total of 50 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Patients with mesothelin positive cancer will be infused the PD-1 antibody expressing mesoCAR-T cells. The modified mesoCAR-T cells can specifically kill mesothelin positive cancer cells and secrete PD-1 antibody, which could enhance the cytotoxicity of mesoCAR-T cells and activate the tumor infiltrating lymphocytes.
China
Shanghai, Shanghai Municipality, China
RECRUITINGIncidence of treatment-related adverse events of infusion of autologous PD-1 antibody expressing mesothelin-targeted CAR-Tcells
Incidence of treatment-related adverse events are assessed using the NCI CTCAE V4.0 criteria.
Time frame: 2 years
Objective response rate (ORR) of the treatment using PD-1 antibody expressing mesoCAR-T cells for advanced solid tumors
Objective response rate (ORR) of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which contains complete response (CR) and partial response (PR).
Time frame: 2 years
Progression free survival
Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.
Time frame: 2 years
Overall survival
Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.
Time frame: 2 years
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