Skin toxicity is directed against murine but not human keratinocytes
(A) NSG mice as shown in Figure 3A implanted subcutaneously with TT cells were injected with non-CAR T cells (top) or P4-10bbz CAR T cells (bottom). (B) Hematoxylin and eosin-stained sections of tail skin from NSG mice bearing TT cell tumors followed by treatment with P4-10bbz CAR T cells prior to gross evidence of skin toxicity (top) and after ulceration (bottom). (C) Sections of skin from an NSG mouse and from a human donor stained with P4-10 antibody. (D) NFAT-GFP reporter Jurkat cells expressing 19bbz, P4-10bbz, or PX44bbz CARs were co-cultured overnight with the indicated target cells or in wells coated with the CD3-specific antibody, OKT3. Cells were then stained with a CD69-specific antibody, and GFP and CD69 expression were analyzed by flow cytometry. A representative of 2 independent experiments is shown. (∗∗p < 0.005, ∗∗∗p < 0.0005, 2-way ANOVA with Tukey’s multiple comparisons test [statistics shown for Mu. KC groups only]). Mu. KC, murine keratinocytes; Hu. KC, human keratinocytes. All error bars indicate 1 standard deviation of the mean.