Extended Data Fig. 10: Intraperitoneal injection of mLiCAR T-cells to reduce ‘on-target off-tumour’ side effects in a syngeneic mouse model of melanoma.
From: Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety
a, Schematic illustration of the mouse model used to evaluate ‘on-target off-tumour’ effects by intraperitoneal (i.p.) injection of B16-OVA-mCD19 tumour cells (3×106). After tumour growth for 3 weeks, WT CAR T cells/UCNPs or LiCAR-T/UCNPs cells that could engage mCD19-B16-OVA cells were subsequently injected into the tumour sites. LiCAR (combination of C + D4.1) T-cells treated mice were subjected to pulsed NIR light stimulation for 3 days (980 nm at a power density of 250 mW/cm2; pulses of 20 sec ON, 5 minutes OFF; 2 h/day). On day 0 and day 3, blood was collected from the retro-orbital sinus by glass capillary from anesthetized mice for B cell quantification. b, On-target off-tumour effects of mWT CAR and mLiCAR T-cells evaluated by the degree of B cell aplasia. Peripheral blood B cells from the WT mCAR or mLiCAR T-cell treated groups were counted and compared on day 0 and day 3. B cells from peripheral blood of healthy mice were used as control. n = 7 biologically independent mice (mean ± s.e.m.). P values were calculated using two-sided unpaired Student’s t-tests.
