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BTEs have proven effective in hematologic malignancies and some solid tumors, yet their potential in glioblastoma (GBM) is largely unexplored. We developed a fully humanized BTE (hBTE) targeting interleukin\u201013 receptor alpha 2 (IL13RA2), a tumor\u2010associated antigen widely expressed in GBM and associated with poor prognosis. In vitro, hBTE activated T cells and induced antigen\u2010dependent cytokine release and cytotoxicity against IL13RA2\u2010positive GBM cells. In vivo, hBTE showed robust target\u2010specific activity and markedly prolonged survival in primary and recurrent GBM xenograft models, without detectable off\u2010target local or systemic toxicity. Beyond GBM, hBTE also exhibited antitumor activity in IL13RA2\u2010expressing solid tumors, demonstrating selective tumor accumulation and therapeutic efficacy in models of breast cancer brain metastases and extracranial lung cancer. This work highlights the therapeutic potential of BTEs in IL13RA2\u2010expressing tumors and establishes a strong preclinical rationale for advancing hBTE therapy toward clinical translation in GBM and other tumors.<\/jats:p>","DOI":"10.1002\/advs.202522391","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:09:32Z","timestamp":1777536572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors"],"prefix":"10.1002","volume":"13","author":[{"given":"Joseph T.","family":"Duffy","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"},{"name":"Department of Pathology Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Martin\u2010Regalado","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt E.","family":"Haupt","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob R.","family":"Pogue","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Fierro","family":"Cota","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markella","family":"Zannikou","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Misener","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera P.","family":"Krymskaya","sequence":"additional","affiliation":[{"name":"Department of Medicine Perelman School of Medicine University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"McCortney","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Miska","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Northwestern University  Chicago IL USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Horbinski","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine &amp; 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