Preclinical efficacy of DLL3 targeted CAR T cells in neuroblastoma
Presenter: Salvatore Aspromonte, BS;MD Session: Immunotherapies in Pediatric Cancers Time: 4/22/2026 9:00:00 AM → 4/22/2026 12:00:00 PM
Authors
Salvatore M. Aspromonte , Tamar Feinberg , Ali Cihan , Samantha Brosius , Armaan H. Siddiquee , Dylan Domenico , Daoqi You , Shakeel Modak , Kevin J. Curran , Andrew L. Kung , Anthony Daniyan , Filemon Dela Cruz Memorial Sloan Kettering Cancer Center, New York, NY
Abstract
Background: Neuroblastoma (NBL), the most common extracranial solid tumor in children, accounts for 15% of pediatric cancer deaths, and survival after relapse remains Methods: DLL3 expression was assessed in NBL patient samples and PDX models by RNA sequencing, immunohistochemistry (IHC), and flow cytometry. IL-18-armored DLL3 CAR T cells were tested in vitro against NBL cell lines across multiple effector-to-tumor (E:T) ratios. Cumulative killing was compared using Vardi’s test for area-under-the-curve analysis, and Wilcoxon rank-sum tests evaluated differences at individual E:T ratios. Results: RNA sequencing of pediatric solid tumors treated at MSK (n=540) showed that NBL (n=109) had the highest DLL3 transcript levels relative to other non-CNS tumors (0-19.7 TPM; median 0.38). In NBL patient samples, IHC (n=31) demonstrated DLL3 protein expression (H-score ≥10, range 10-300, median 100) in 52% (16/31) with strong transcript-protein concordance (Spearman r=0.847, p=2×10 -9 ). In NBL PDX models, DLL3 protein expression was detected in 63% (19/30), with H-scores ranging 10-123 (median 73). Flow cytometry across five PDX models spanning H-scores 7-105 showed DLL3 surface expression on 25-88% of tumor cells, confirming antigen accessibility. IL-18-armored DLL3-CAR T cells exhibited significantly greater cumulative cytotoxicity than untransduced T cells against two DLL3+ NBL cell lines, SK-N-DZ (51% DLL3+, p=0.03) and SK-N-SH (29% DLL3+, p=0.03), with activity across multiple E:T ratios (p Conclusions: DLL3 is expressed in a subset of NBL patient tumors and PDX models and is accessible for CAR targeting. IL-18-armored DLL3-directed CAR T cells show strong in vitro cytotoxicity against DLL3+ NBL models. In vivo testing in a DLL3+ NBL PDX is underway. These findings support DLL3 as a promising immunotherapeutic target and justify further development of DLL3-directed CAR T therapy for NBL.
Disclosure
S. M. Aspromonte, None.. T. Feinberg, None.. A. Cihan, None.. S. Brosius, None.. A. H. Siddiquee, None.. D. Domenico, None.. D. You, None.. S. Modak, None. K. J. Curran, Novartis Independent Contractor, ). Turn Bio g., Board of Directors, non-salaried role), Stock. PromiCell g., Board of Directors, non-salaried role), Stock. Cellectis ). Atara Bio ). A. L. Kung, Karyopharm Therapeutics g., Board of Directors, non-salaried role). DarwinHealth g., Board of Directors, non-salaried role). Isabl g., Board of Directors, non-salaried role), Stock, Patent. Labcorp Other Intellectual Property. A. Daniyan, Biolumina Independent Contractor. Caribou Biosciences, Inc Patent. Hierax Therapeutics, Inc. Independent Contractor. NomoCan Pharmaceuticals LLC Independent Contractor. PromiCell Therapeutics, Inc. g., Board of Directors, non-salaried role), Stock, Patent. Shoreline Biosciences, Inc. Independent Contractor. Syndax Patent. Tigen Pharma SA Patent. F. Dela Cruz, Eisai ). Y-mAbs Therapeutics ).
Cited in
Control: 803 · Presentation Id: 1770 · Meeting 21436