In this study, investigators have developed a novel CAR T cell system targeting both mesothelin (MSLN) antigen-expressing cells and CD40 ligand-expressing cells, termed as CD40 ligand expressing MSLN-CAR T. Preclinical study demonstrated that the CD40 ligand expressing MSLN-CAR T cells possess more powerful antitumor activity than previously reported MSLN-CAR T cells in animal models. In this clinical trial, at least 12 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD40 ligand expressing MSLN-CAR T cell therapy (1×10^6 cells/kg, 3×10^6 cells/kg, 6×10^6 cells/kg) according to the 3+3 principle, in order to evaluate the safety, feasibility and preliminary antitumor activity of CD40 ligand expressing MSLN-CAR T cells. In dose expansion period, additional 10 to 18 patients will be enrolled to receive CD40 ligand expressing MSLN-CAR T cell therapy at dose of recommended phase 2 dose (RP2D), which is determined by data from dose escalation period, including dose limiting toxicities, maximum tolerated dose, pharmacokinetics/pharmacodynamics, efficacy and other parameters, in order to further assess the safety and efficacy profiles of CD40 ligand expressing MSLN-CAR T cell therapy.
In preclinical study, investigators have demonstrated that the newly developed CD40 ligand expressing MSLN-CAR T cells possess more powerful antitumor activity than previously reported MSLN-CAR T cells in animal models. In this clinical trial, at least 12 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD40 ligand expressing MSLN-CAR cell therapy according to the 3+3 principle. In dose expansion period, additional 10 to 18 patients will be enrolled to receive CD40 ligand expressing MSLN-CAR T cell therapy at dose of RP2D.