Abstract
Objectivechordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic options of skull base chordomas.Methodswe profiled 45 skull base chordoma clinical samples by immunohistochemistry for the expression of six CAR-Targets (PD-L1, B7-H3, B7-H4, VISTA, HER2 and HER3). In addition, we generated B7-H3 targeted CAR-T-cells and evaluated their antitumor activities in vitro.ResultsWe found that B7-H3 was positively stained in 7 out of 45 (16%) chordoma samples and established an expression hierarchy for these antigens (B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4). We then generated a B7-H3 targeted CAR vector and demonstrated that B7-H3-CAR-T-cells recognized antigen positive cells and exhibited significant antitumor effects, including suppression of tumor spheroid formation, CAR-T-cell activation and cytokine secretion.ConclusionsOur results support B7-H3 might serve as a promising target for CAR-T-cell therapies against chordomas.
Highlights
Chordoma is a rare tumor arising from notochordal remnant, mainly involving the skull base, sacrococcygeal area and vertebral bodies [1]
The antibodies used to identify the phenotype of Chimeric antigen receptor (CAR)-T cells included CD3-allophycocyanin (APC)-CY7 HIT3a, perforin-APC B-D48, GZMB-PE QA16A02, LAG3-FITC 11C3C65, TIM3-BV711 F38-2E2, and PD-1-BV605 NAT105
To identify potential CAR-Targets for chordoma, we evaluated 6 tumor antigens
Summary
Chordoma is a rare tumor arising from notochordal remnant, mainly involving the skull base, sacrococcygeal area and vertebral bodies [1]. Chordoma is often not completely resectable and shows a high recurrence rate and shortened survival, especially in skull base where complete tumor resection is often not possible because of the proximity of cranial nerves [4, 5]. There is a great need for efficient therapies that reduce recurrence and progression. Chimeric antigen receptor (CAR) T cells are patient derived T cells that have been genetically engineered to express an engineered synthetic receptor for targeting and killing cancer cell [6]. With the unprecedented success of CAR-T cells in blood cancer, a growing number of studies have
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