The first challenge is tumor heterogeneity, defined as the expression of different antigens among the subpopulations of a tumor, which contributes to antigen escape.42,46,53–55 Antigen escape refers to tumors losing expression of a targeted antigen (eg, loss of IL-13Rα2 following IL-13Rα2-CAR-T therapy or EGFRvIII loss following EGFRvIII-CAR-T therapy).43,46 By employing single-cell RNA sequencing (RNA-seq) to profile cells from 5 GBM samples, Patel et al. demonstrated GBM intratumoral heterogeneity based on transcriptional programming and degree of stemness. This evidence concerns the gene IL13RA2 and glioblastoma.