CAR T
Published on August 20, 2024
GPC2 CAR T-cells as a potential therapeutic strategy for intraocular and CNS metastatic retinoblastomas
by AACR
Pascual-Pasto G, McIntyre B, Giudice AM, et al. Targeting GPC2 on Intraocular and CNS Metastatic Retinoblastomas With Local and Systemic Delivery of CAR T-Cells. Clinical Cancer Research. 2024; (doi: 10.1158/1078-0432.CCR-24-0221).
Chimeric antigen receptor (CAR) T-cells aimed at glypican-2 (GPC2) could delay ocular loss in patients with metastatic retinoblastoma, according to research with human samples and mouse models. GPC2 is present on retinoblastoma tumors but not on normal tissues of the retina, making it easier for CAR T cells to gravitate toward tumor-bearing eyes. In intraocular models, tumor-specific expression correlated to longer ocular survival. Functional studies revealed that GPC2-directed CARs mediate retinoblastoma cell cytotoxicity and improve T-cell proliferation and polyfunctionality, especially when working through the 4-1BB co-stimulatory domain (GPC2.BBz) versus the CD28 co-stimulatory domain. Enhanced persistence of the GPC2.BBz CAR T cells was associated with marked tumor regression compared with control CARs. In central nervous system (CNS) retinoblastoma models, the CAR T cells were activated in retinoblastoma-involved CNS tissue, which led to tumor regression and significantly prolonged overall mouse survival.
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