Despite significant responses in patients with various solid cancers treated with CAR T cells, such as disialoganglioside GD2 in neuroblastoma (95) and H3K27M-mutated diffuse midline gliomas (96), mesothelin (MSLN) in mesothelioma (97), claudin 18.2 (CLDN18.2) in pancreatic cancer (98), and IL13Rα2 in combination with EGFR in glioblastoma multiforme (99), CAR-based therapies for solid cancers face major limitations and challenges. The gene discussed is MSLN; the disease is mesothelioma.