Immunotherapy for bloodcancer: Remote destruction of tumor cells demonstrated institutpasteur naturecancer
. T cells were then subjected to two rounds of spin-infections using retroviral supernatant and 8 μg mlhIL-2 . For in vivo imaging experiments, CAR T cells were retrovirally transduced to express GFP. For comparable in vitro activation, IFN-γ-deficient T cells and their WT counterparts were supplemented with 100 ng mlof IFN-γ . CAR transduction efficacy was routinely >80%; in cases of lower efficacy, transduced cells were isolated using the hCD34 positive selection kit .
. B-cell tumors developed initially in the bone marrow and became detectable in the blood by day 6–7. At this time, CAR T cells were injected i.v. For the solid tumor model, tumors were established by injecting 0.5 × 10B16-CD19 cells subcutaneously in the flank of sublethally irradiated mice. Tumors were allowed to grow for 10 d at which time CAR T cells were injected intravenously. Starting tumor volumes were normalized between treatment groups.
For in vitro IFN-γ exposure on tumor cells, different IFN-γ concentrations were used ranging from 0.005–1,000 ng mlfor the indicated time. For in vivo cytokine supplementation studies, murine IFN-γ was delivered twice i.v. for 2 d starting 7–8 d after tumor inoculation.To assess the ability of IFN-γ to diffuse and induce tumor killing at distance, a Transwell assay was set up. Tumor cells and CAR T cells were co-cultured in the upper chamber of a 24-well Transwell plate .
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