{"entity":{"id":"il2-anti-gd2-caution","kind":"pairing","name":"Caution: IL-2 added to anti-GD2 therapy","aka":[],"tldr":"Interleukin-2 was part of the original immunotherapy package but a large European trial showed it adds toxicity and no benefit, so it has been dropped.","summary":"Interleukin-2 was part of the original anti-GD2 immunotherapy package for high-risk neuroblastoma, and this caution pairing records why it has been dropped. In the R2 randomised comparison of the SIOPEN HR-NBL1 trial, adding subcutaneous IL-2 to dinutuximab beta produced no meaningful improvement in event-free survival but far more severe toxicity. The rationale is that IL-2 expands regulatory T cells and causes capillary leak, whereas the NK-cell-mediated antibody-dependent cytotoxicity that the anti-GD2 antibody relies on is sufficiently supported by GM-CSF. European protocols omit IL-2 and the Children's Oncology Group has since removed it as well in ANBL1531, so the combination now stands as a warning example within the broader cytokine therapy record.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01704716: SIOPEN HR-NBL1","url":"https://clinicaltrials.gov/study/NCT01704716"}],"tags":[],"related":[],"cancers":["neuroblastoma","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["dinutuximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hr-nbl1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"dinutuximab","b":"cytokine-therapy","rationale":"IL-2 expands regulatory T cells and causes capillary leak; NK-mediated ADCC is sufficiently supported by GM-CSF.","evidence":"Randomised phase 3 (HR-NBL1).","pairingType":"caution"},"route":"/pairings/il2-anti-gd2-caution/","neighbours":{"cancer":[{"id":"neuroblastoma-high-risk","kind":"cancer","name":"High-risk neuroblastoma","route":"/cancers/neuroblastoma-high-risk/"},{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"}],"drug":[{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"}],"trial":[{"id":"hr-nbl1","kind":"trial","name":"SIOPEN HR-NBL1","route":"/trials/hr-nbl1/"}],"technology":[{"id":"cytokine-therapy","kind":"technology","name":"Cytokines & engineered cytokines","route":"/technologies/cytokine-therapy/"}]}}