Abstract B017: Precision Nanotherapy for the Treatment of Progressive Neuroblastoma

Deadly progressive neuroblastoma (pNB) that defy current clinical therapy is a devastating pediatric malignancy with frequent relapses and negligible <2% long-term survival. Appropriately, global efforts are in place to identify new and effective molecular-targeted maintenance therapies. Owing to our recent findings on the function of Retinal Degeneration 3 (RD3) in NB pathogenesis, particularly in therapy resistance and disease evolution, we aimed to develop and characterize RD3-targeted therapeutic strategy for pNB. Herein, we archived novel targeted therapeutic deliverables and assessed their efficacy in treating clinical therapy defying pNB, as well evaluated their safety profiles. Five unique RD3 peptides were synthesized, labeled, capped, and assessed for their cellular homing capacities. NB targeted (GD2) RD3-peptide loaded immunoliposomes (RD3Þ[GD2]IL) were constructed and characterized for size distribution (NT Analyzer NS300), encapsulation efficacy (absorbance) and structural integrity (TEM). Xenografts developed in athymic nude mice with pNB cells derived from retroperitoneum (CHLA-20) were treated with plain liposomes or RD3Þ[GD2]IL 1 through 5 (i.v. 5mM) 3 days/week for 4 weeks were assessed for tumor regression, differentiation, and normal tissue toxicity if any. All RD3Þ[GD2]IL formulations demonstrated significant anti-tumor efficacy compared to controls. Micromorphological analysis indicated no defined toxicity in health tissues and major organs. Relatively, RD3Þ[GD2]IL-3 displayed high efficacy with substantial reduction in tumor volume . Histopathology revealed that tumors treated with RD3Þ[GD2]IL-3 exhibited a well-differentiated phenotype in the residual tumor, in stark contrast to the poorly differentiated morphology observed in control groups. Together, the results present a novel, targeted nano therapy that effectively suppresses pNB growth and restores differentiation. RD3Þ[GD2]IL-3 demonstrates the ability to both inhibit pNB progression and promote tumor cell dedifferentiation, the two critical challenges in the treatment of resistant/refractory disease. When integrated with existing intensive multi-modal clinical therapies, RD3Þ[GD2]IL-3 holds the potential to redefine the therapeutic landscape and deliver desirable clinical benefit in a setting where options are currently not available. Funding: This work was funded by the DoD-CA-210339, OCAST-HR19-045, NIH P20GM103639 to Dr. Aravindan and NCI-P30 CA225520, OK-TSET-R23-03 and NIGMS P30GM154635 awarded to the OU Health SCC. Citation Format: Loganayaki Periyasamy, Poorvi Subramanian, Sheeja Aravindan, Afsana Parveen Jahir Hussain, Natarajan Aravindan. Precision Nanotherapy for the Treatment of Progressive Neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2): nr B017.