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 express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting MUC1 in adult patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors.
This study will be conducted using a phase I/II trial design to assess the safety and efficacy of the CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T for patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors. MUC1-CAR-T can specificly and effectively kill the MUC1 positive cancer cells, CTLA4 and PD-1 antibodies 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 CTLA-4 and PD-1 antibodies and chimeric antigen receptor targeting MUC1. Cells are proliferated in culture and returned to the patients by venous transfusion. A total of 40 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
40
Every cycle, peripheral blood mononuclear cells (PBMC) are collected on day 0, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of CTLA-4 and PD-1 antibodies expressing MUC1 targeted CAR-T cells at (2-5) ×10\^7 cells/kg from day 18 to day 19 (±2 days). 2 cycles are regarded as a treatment period.
Ningbo No.5 Hospital (Ningbo Cancer Hospital)
Ningbo, Zhejiang, China
RECRUITINGSafety of infusion of autologous CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells
Determine the toxicity profile of CTLA4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Time frame: 2 years
The efficacy of the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells for advanced solid tumors
The efficacy of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).
Time frame: 2 years
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