{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T22:30:03Z","timestamp":1786487403644,"version":"build-2736575974"},"reference-count":36,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"23","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>We developed a novel approach to treat newly diagnosed glioblastoma (GBM) using genetically modified gamma-delta (\u03b3\u03b4) T cells following the forced upregulation of stress-associated targets on tumor cells. We leveraged the temozolomide (TMZ)-induced activation of the DNA damage response pathway to transiently upregulate the natural killer ligand (NKG2D-L) targets on GBM. Manufactured \u03b3\u03b4 T cells are engineered to be resistant to alkylating chemotherapies, including TMZ, through insertion of a methylguanine-DNA methyltransferase (MGMT)\u2013expressing lentivector (DeltEx drug-resistant immunotherapy\u2014DRI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      A total of 23 patients were enrolled, and 13 were treated (62% male; median age 66 years [range, 21-75]; 92% isocitrate dehydrogenase wild type (IDH-WT), 54% MGMT unmethylated, 46% subtotal resection). Cohorts 1, 2, and 3 received 1, 3, or up to 6 doses, respectively (1 \u00d7 10\n                      <jats:sup>7<\/jats:sup>\n                      DRI cells\/dose), using a Rickham catheter, which was placed into the resection cavity. The DRI cells were dosed in combination with 150 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      intravenous (IV) TMZ once per day on Day (D) 1 of each maintenance cycle, which was followed by 4 days of oral TMZ.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>No dose-limiting toxicities were seen nor were any occurrences of cytokine release syndrome (CRS) or neurotoxicity (immune effector cell\u2013associated neurotoxicity syndrome) observed. The median follow-up of patients who received DRI \u03b3\u03b4 T cells was 15.6 months. For Cohort 1 patients who received a single dose of DRI \u03b3\u03b4 T cells, the median progression-free survival (mPFS) was 8.0 months; the median PFS was 9.9 months for all patients and 16.1 months for patients who received repeated doses in Cohorts 2 and 3. The median overall survival for all patients was 15.6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>To date, all patients had manageable toxicity with outpatient treatment and a continued encouraging trend in outcomes from repeated investigational treatments with intracranially delivered, longitudinal DRI \u03b3\u03b4 T cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02463","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:59:22Z","timestamp":1783540762000},"page":"2211-2220","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Intracranial Injection of Investigational Ex Vivo Expanded and Activated Gamma-Delta T Cells Engineered With a Methylguanine-DNA Methyltransferase\u2013Expressing Lentivector in Patients With Primary 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