Neuroblastoma

P1/2, N=100, Recruiting, Shenzhen Geno-Immune Medical Institute | Trial completion date: Dec 2023 --> Dec 2030 | Trial primary completion date: Nov 2020 --> Dec 2029

This pilot study suggests that irinotecan may modulate key immune checkpoints in neuroblastoma. These results supports further investigation of rational chemo-immunotherapy combinations, including GD2 and CD47-targeted combination strategies.

Consequently, the direct in vivo evidence for the role of NPY in metastasis and clinical data associating the expression of NPY and its receptor with adverse disease phenotypes are growing. Understanding the mechanisms underlying these effects may lead to the design of novel therapeutic approaches targeting the NPY system to prevent cancer progression.

This study systematically elucidated the crucial role of lipid metabolic reprogramming in the pathogenesis of HR MYCN-NA NB. These findings provide critical insight for uncovering the mechanisms underlying NB progression and for identifying potential therapeutic targets.

While feasible to manufacture in a heavily pretreated population, L1CAM may not be an appropriate target in neuroblastoma. Additional engineering strategies may be needed to prevent toxicity and provide durable anti-tumor effects.

P1, N=23, Terminated, Y-mAbs Therapeutics | N=60 --> 23 | Trial completion date: Apr 2027 --> Mar 2026 | Recruiting --> Terminated | Trial primary completion date: Mar 2027 --> Mar 2026; Decision by Sponsor

These findings support a front-loaded 177Lu-DOTATATE strategy to maximise tumour irradiation while maintaining exposure to risk organs within safety limits. Accordingly, the LuDO-N protocol has been amended to increase administered activity to 400 MBq/kg in the first fraction for subsequent patients. Together, this work contributes to the ongoing optimisation of dosimetry-guided and intensified treatment strategies for SSTR-targeted molecular radiotherapy for high-risk neuroblastoma.

High-risk tumors were enriched for translational and ribosome biogenesis pathways, whereas low-risk tumors were enriched for adaptive immune activation programs. Cross-context transcriptomic integration identified a minimal ALK-associated three-gene signature that reproducibly predicts NB outcomes and reflects distinct underlying biological states, supporting its potential value for risk stratification and hypothesis-driven therapeutic development.

Collectively, our findings uncover a novel mechanism by which doxorubicin enhances NB tumor susceptibility to γδT-cell-mediated killing through ULBP1 up-regulation. This study provides a strong rationale for combining chemotherapy with γδT-cell-based immunotherapy to improve outcomes in high-risk NB patients.

Although the primary endpoint was not met, BA showed a manageable safety profile and a subset of patients derived clinical benefit with prolonged stable disease, including one patient with a complete metabolic response. This first clinical trial of systemic therapy in R/M ONB serves as proof of clinical trials feasibility in this setting and supports further investigation of combinatorial immunotherapy strategies in this patient population. Trial registration ClinicalTrials.gov Identifier: NCT05012098, https://clinicaltrials.gov/ct2/show/NCT05012098. Registered 18 August 2021.

This signaling cascade suppresses NF-κB-mediated proinflammatory pathways, evidenced by diminished NF-κB activation and reduced secretion of inflammatory mediators (interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)), ultimately promoting SH-SY5Y survival. Our findings establish glycoRNAs as critical mediators of intercellular signaling with therapeutic potential in neuroinflammation.

P1, N=3, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=23 --> 3