{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:04:59Z","timestamp":1790064299148,"version":"4.0.1"},"reference-count":25,"publisher":"Aboutscience Srl","issue":"1","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","award":["Centers for Excellence in Developmental Therapeutics"],"award-info":[{"award-number":["Centers for Excellence in Developmental Therapeutics"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1TR001880"],"award-info":[{"award-number":["TL1TR001880"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Circ Biomark"],"abstract":"<jats:p>Introduction: GD2 is a ganglioside expressed on neuroblastoma cell membranes and shed into the circulation, where it primarily circulates bound to low-density lipoprotein (LDL). We questioned whether LDL-bound GD2 could interfere with the binding of therapeutic anti-GD2 monoclonal antibodies (like dinutuximab) to neuroblastoma cells.Methods: The GD2-expressing neuroblastoma cell line IMR5 was stained with an anti-GD2 antibody tagged with allophycocyanin (APC) at the lowest possible saturating concentration, and mean fluorescence intensity was measured by flow cytometry after in vitro exposure to GD2-LDL or free GD2 at multiple concentrations. Control experiments assessed the ability of GD2-expressing and GD2-non-expressing cells to compete for anti-GD2-APC antibodies with IMR5 cells.Results: Free and LDL-bound GD2 reduced anti-GD2-APC antibodies\u2019 binding to IMR5 cells in vitro in a concentration-dependent manner. At physiologically relevant concentrations, LDL-bound GD2 blocked antibody binding to IMR5 to a greater extent than free GD2, including at 100 nM, a concentration below median GD2 concentrations in patients with high-risk neuroblastoma. At higher concentrations, LDL-bound GD2 inhibited antibody binding to IMR5 by up to 92.6%, whereas the same concentration of free GD2 only decreased antibody binding by 56.6%Conclusions: At concentrations found in patients with high-risk neuroblastoma, both free GD2 and LDL-bound GD2 blocked anti-GD2 antibody binding to neuroblastoma cells. These data suggest that circulating GD2-LDL could impact the efficacy of therapeutic anti-GD2 antibodies administered to patients with a high disease burden during induction therapy or at relapse and may have therapeutic implications for GD2-directed adoptive cellular therapies.<\/jats:p>","DOI":"10.33393\/jcb.2026.3797","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:16:56Z","timestamp":1790061416000},"page":"69-77","source":"Crossref","is-referenced-by-count":0,"title":["Circulating free and low-density lipoprotein-bound GD2 can compete in vitro with neuroblastoma cells for binding therapeutic anti-GD2 antibodies"],"prefix":"10.33393","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3962-6740","authenticated-orcid":false,"given":"Christina","family":"Turn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Busch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Toland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Bassiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Hogarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8117-6926","authenticated-orcid":false,"given":"Frank M.","family":"Balis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"18642","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"20807","unstructured":"Wu ZL, Schwartz E, Seeger R, Ladisch S. Expression of GD2 ganglioside by untreated primary human neuroblastomas. Cancer Res. 1986;46(1):440-443. PMID:3940209"},{"key":"20808","doi-asserted-by":"crossref","unstructured":"Mohd AB, Mohd OB, Alabdallat YJ, et al. Safety and efficacy of dinutuximab in the treatment of neuroblastoma: a review. J Res Med Sci. 2023;28(1):71. https:\/\/doi.org\/10.4103\/jrms.jrms_727_22 PMID:38116487","DOI":"10.4103\/jrms.jrms_727_22"},{"key":"20809","doi-asserted-by":"crossref","unstructured":"Yu AL, Gilman AL, Ozkaynak MF, et al.; Children\u2019s Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363(14):1324-1334. https:\/\/doi.org\/10.1056\/NEJMoa0911123 PMID:20879881","DOI":"10.1056\/NEJMoa0911123"},{"key":"20810","doi-asserted-by":"crossref","unstructured":"Mody R, Naranjo A, Van Ryn C, et al. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017;18(7):946-957. https:\/\/doi.org\/10.1016\/S1470-2045(17)30355-8 PMID:28549783","DOI":"10.1016\/S1470-2045(17)30355-8"},{"key":"20811","doi-asserted-by":"crossref","unstructured":"Kushner BH, Cheung IY, Modak S, et al. Humanized 3F8 anti-GD2 monoclonal antibody dosing with granulocyte-macrophage colony-stimulating factor in patients with resistant neuroblastoma: a phase 1 clinical trial. JAMA Oncol. 2018;4(12):1729-1735. https:\/\/doi.org\/10.1001\/jamaoncol.2018.4005 PMID:30326045","DOI":"10.1001\/jamaoncol.2018.4005"},{"key":"20812","doi-asserted-by":"crossref","unstructured":"Ladisch S, Wu ZL, Feig S, et al. Shedding of GD2 ganglioside by human neuroblastoma. Int J Cancer. 1987;39(1):73-76. https:\/\/doi.org\/10.1002\/ijc.2910390113 PMID:3539825","DOI":"10.1002\/ijc.2910390113"},{"key":"20813","doi-asserted-by":"crossref","unstructured":"Balis FM, Busch CM, Desai AV, et al. The ganglioside GD2 as a circulating tumor biomarker for neuroblastoma. Pediatr Blood Cancer. 2020;67(1):e28031. https:\/\/doi.org\/10.1002\/pbc.28031 PMID:31612589","DOI":"10.1002\/pbc.28031"},{"key":"20814","doi-asserted-by":"crossref","unstructured":"Busch CM, Balis FM. Age-dependent reference intervals in children for the disialoganglioside, GD2, a circulating tumor biomarker for the childhood cancer, neuroblastoma. Clin Biochem. 2022;101:1-4. https:\/\/doi.org\/10.1016\/j.clinbiochem.2021.12.007 PMID:34929151","DOI":"10.1016\/j.clinbiochem.2021.12.007"},{"key":"20815","unstructured":"Balis FM, McCully CL, Busch CM, et al. Pharmacokinetics of the disialoganglioside, GD2, a"},{"key":"20816","doi-asserted-by":"crossref","unstructured":"circulating tumor biomarker for neuroblastoma, in nonhuman primates. J Circ Biomark. 2021;10:26-29. https:\/\/doi.org\/10.33393\/jcb.2021.2329 PMID:34898668","DOI":"10.33393\/jcb.2021.2329"},{"key":"20817","unstructured":"Valentino LA, Ladisch S. Localization of shed human tumor gangliosides: association with serum lipoproteins. Cancer Res. 1992;52(4):810-814. PMID:1737341"},{"key":"20818","doi-asserted-by":"crossref","unstructured":"McNerney KO, Karageorgos S, Ferry GM, et al. TH-MYCN tumors, but not tumor-derived cell lines, are adrenergic lineage, GD2+, and responsive to anti-GD2 antibody therapy. OncoImmunology. 2022;11(1):2075204. https:\/\/doi.org\/10.1080\/2162402X.2022.2075204 PMID:35646475","DOI":"10.1080\/2162402X.2022.2075204"},{"key":"20819","doi-asserted-by":"crossref","unstructured":"Morini M, Barco S, Ardito M, et al. 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