Immunotherapy with CAR T cells for pediatric solid and
brain tumors is constrained by available targetable
antigens.
Cancer-specific exons (CSE) present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-
cancer fashion. To identify CSE targets, we analyzed 1,532
RNA-seq datasets from 16 types of pediatric solid and
brain tumors for comparison with normal tissues using a newly developed workflow. We found 2,933 exons in 157 genes encoding
proteins of the surfaceome or matrisome with high
cancer specificity either at the gene (n=148) or the alternatively spliced (AS)
isoform (n=9) level. Expression of selected AS targets, including the EDB domain of FN1 (EDB), and gene targets, such as COL11A1, were validated in pediatric PDX
tumors. We generated CAR T cells specific to EDB or COL11A1 and demonstrated that COL11A1-CAR T-cells have potent antitumor activity. The full target list, explorable via an interactive web portal (https://cseminer.stjude.org/), provides a rich resource for developing
immunotherapy of pediatric solid and
brain tumors using gene or AS targets with high expression specificity in
cancer.