Abstract Tumors of the pineal region are rare brain tumors originating from the pineal cells, affecting predominantly children and young adults, and collectively accounting for less than 1% of all pediatric brain tumors. Based on histology, they can be classified as: pineocytoma (Pin-Cyt), pineal parenchymal tumors of intermediate differentiation (PPTID), papillary tumors of the pineal region (PTPR), and pineoblastoma (PB). Due to their high rate of recurrence and tendency to metastasize to the leptomeninges, the majority of pineoblastomas display a very dismal prognosis. The rarity of these tumors makes it difficult to generate reliable preclinical models, thereby hindering our ability to comprehensively understand their tumor biology and identify potential therapeutical targets. We generated two patient-derived xenograft (PDX) models, from a 21-year-old female pineoblastoma patient (CBTP-115) and a 22-year-old male PPTID patient (CBTP-165) respectively. Both models have been passed more than twice in NOD-SCID mice, with an average survival time of 3 months for both CBTP-115 and CBTP-165. Considering the reproducibility of the models, we used flow cytometry and RT-PCR to screen for relevant CAR-T cell targets, such as B7-H3, IL13R2A, GPC2, Epha2, HER2, EGFR, PROM1, and B4GALNT1 which is involved in the synthesis of GD2. Our preliminary data confirmed the expression of B7-H3, GPC2, HER2, and PROM1, suggesting the potential use of cell therapy for these subsets of tumors. To our knowledge, no other reproducible models have been used to identify potential CAR-T cell targets in pineal tumors.
Cocito et al. (Fri,) studied this question.