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Multiomic analysis of the biopsy cores revealed therapeutic effects, including longitudinal and spatial reshaping of the rGBM\u2019s microenvironment, expansion of new T cell tissue-resident effector memory clonotypes against CAN-3110 epitopes and other undetermined antigens, and expression of human leukocyte antigen (HLA)\u2013presented immunopeptides, including cancer testis antigens. Moreover, serial integrated multimodal analyses provided evidence of therapeutic responses to CAN-3110 despite traditional magnetic resonance imaging indicating progression. Clinically, the two treated patients achieved a pathologic response or stable clinical disease, respectively. These results show the value of longitudinal tissue sampling to understand rGBM\u2019s evolution during administration of an investigational therapy.<\/jats:p>","DOI":"10.1126\/scitranslmed.adv2881","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:59:46Z","timestamp":1759946386000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-9875","authenticated-orcid":true,"given":"Alexander L.","family":"Ling","sequence":"first","affiliation":[{"name":"Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-0671","authenticated-orcid":true,"given":"Jennifer","family":"Gantchev","sequence":"additional","affiliation":[{"name":"Surgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5028-3833","authenticated-orcid":true,"given":"Sreyashi","family":"Basu","sequence":"additional","affiliation":[{"name":"James P. 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