Fig. 2: Treatment with CT041-scFv CLDN18.2-targeted CAR T cells leads to intolerable on-target/off-tumor toxicity.
From: Modeling and addressing on-target/off-tumor toxicity of claudin 18.2 targeted immunotherapies
NSG-DKO mice bearing OE19 xenografts were left untreated (UTD, n = 4) or treated on day 13 with 1 × 106 CT041-scFv (n = 4) or BCMA-scFv (n = 3) CAR T by tail vein. A Tumor volume over time, comparing BCMA-scFv and CT041-scFv CAR treatment. Data are presented as mean ± SEM. B Body weight, comparing BCMA-scFv and CT041-scFv. Animals reached humane endpoint if body weight declined by 20% or due to tumor progression. Data are presented as mean ± SEM. C Overall survival. D Stomach from a CT041-scFv-treated animal at the time of sacrifice due to toxicity. H&E shows atrophy of normal architecture and inflammation (scale bar 100 µm). E–H Tissue was stained via immunofluorescence for E CLDN18.2, F human CD3, G epithelial marker, PANCK. DAPI identifies cell nuclei (blue). H Merge demonstrates strong gastric CLDN18.2 expression with colocalization of human CD3+ T cells. Scale bars 20 µm. D–H representative of n = 2 mice. A, B unpaired, two-sided t-test. C Log-rank Mantel–Cox test, *p < 0.05; **p < 0.01.
