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Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I\/II study in recurrent\/refractory patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The 3+3\u2009dose escalation phase I study (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02173093\">NCT02173093<\/jats:ext-link>) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160\u00d710<jats:sup>6<\/jats:sup> GD2BATs\/kg\/infusion complemented by daily interleukin-2 (300,000 IU\/m<jats:sup>2<\/jats:sup>) and twice-weekly granulocyte macrophage colony-stimulating factor (250 \u00b5g\/m<jats:sup>2<\/jats:sup>). The phase II segment focused on patients with NB at the dose 3 level of 160\u00d710<jats:sup>6<\/jats:sup> GD2BATs\/kg\/infusion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2\u20133 fevers\/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-\u03b3) EliSpots, Th1 cytokines, and\/or chemokines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study demonstrated the safety of GD2BATs up to 160\u00d710<jats:sup>6<\/jats:sup>\u2009cells\/kg\/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-008744","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T02:05:18Z","timestamp":1711073118000},"page":"e008744","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Targeting refractory\/recurrent neuroblastoma and osteosarcoma with anti-CD3\u00d7anti-GD2 bispecific antibody armed T cells"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct02173093","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02173093","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1403-1399","authenticated-orcid":false,"given":"Maxim","family":"Yankelevich","sequence":"first","affiliation":[{"name":"St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, USA"},{"name":"Children's Hospital of Michigan, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Thakur","sequence":"additional","affiliation":[{"name":"University of Virginia Cancer Center, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakeel","family":"Modak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Chu","sequence":"additional","affiliation":[{"name":"Children's Hospital of Michigan, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Taub","sequence":"additional","affiliation":[{"name":"Children's Hospital of Michigan, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alissa","family":"Martin","sequence":"additional","affiliation":[{"name":"Children's Hospital of Michigan, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Schalk","sequence":"additional","affiliation":[{"name":"University of Virginia Cancer Center, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Schienshang","sequence":"additional","affiliation":[{"name":"University of Virginia Cancer Center, Charlottesville, Virginia, 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