CAR T Cells in Mesothelin Expressing Cancers

This is a Phase I study evaluating the safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells with and without lymphodepleting chemotherapy. * Cohort 1 (N=3-6): will receive a single dose of 1-3x10\^7 huCARTmeso cells/m\^2 on day 0 without any conditioning chemotherapeutic regimen. * Cohort 2 (N=3-6): will receive a single dose of 1-3x10\^7 huCARTmeso cells/m\^2 on day 0, following a flat dose of 1 gram/m2 of cyclophosphamide administered 2-4 days prior to huCARTmeso cells (day -4 to day -2). * Cohort 3 (N=3-6): will receive a single dose of 1-3x10\^8 /m\^2 lentiviral transduced huCART-meso cells on day 0 without any conditioning chemotherapeutic regimen. \*\*Cohort 3 permanently closed\*\* * Cohort 4 subjects (N=3-6) will receive a single dose of 1-3x10\^8 /m\^2 lentiviral transduced huCART-meso cells on day 0, following a flat dose of 1 gram/m\^2 of cyclophosphamide administered 2-4 days prior to huCART-meso cells (day -4 to day -2). \*\*Cohort 4 permanently closed\*\* * Cohort 5 (N=up to 6): will receive a single dose of 1-3x10\^7 huCARTmeso cells/m\^2 on day 0 by intrapleural infusion (IP) through an indwelling pleural catheter without any conditioning chemotherapeutic regimen. The safety of this dose level has been established by Cohorts 1 and 2. * Cohort 6 (N=up to 6): will receive a dose of 1-3x10\^7 huCARTmeso cells/m\^2 via IV infusion on Day 0, following a flat dose of 1 gram/m\^2 of cyclophosphamide administered 2-4 days prior to huCART-meso cells (\~Day -4 to -2). This initial infusion may be followed by up to two additional IV infusions of huCART-meso cells at the same dose level, given between 21-42 days apart, if the subject meets eligibility to receive additional infusions. Cyclophosphamide will not be repeated prior to subsequent doses of huCART-meso cells. Enrollment into Cohort 6 will occur in parallel with Cohort 5. * Cohort 7 (N = up to 6): will receive a single dose of 1-3x10\^7 huCART-meso cells/m\^2 via intraperitoneal (i.p.) administration, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day given over 3 days by intravenous infusion. Lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (+/- 1 day) prior to the 1st infusion of huCART-meso cells. This initial i.p. infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart. The subject must meet eligibility to receive additional infusions. Lymphodepleting chemotherapy will not be repeated prior to additional infusions of huCART-meso cells. The Maximum Tolerated Dose (MTD) is defined as the dose at which 0-1 DLT occurs in 6 evaluable subjects tested within the dose range of this study. The maximum tolerated dose has been established as 1-3x10\^7 huCARTmeso cells/m\^2. Adverse events will be collected and evaluated during the protocol specified adverse event reporting period