{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:41:30Z","timestamp":1793320890000,"version":"4.5.0"},"reference-count":10,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,4,20]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Pancreatic cancer remains among the deadliest malignancies, with a 5-year survival of ~13%. Chimeric antigen receptor (CAR) T -cell therapy offers hope, but conventional \u03b1\u03b2 T cells can trigger severe toxicities, including graft-versus-host disease (GvHD) when used for allogeneic therapy. By contrast, \u03b3\u03b4 T cells recognize tumors without MHCmajor histocompatibility complex restriction and are unlikely to cause GvHD, making them attractive candidates for \u201coff-the-shelf\u201d immunotherapy. Li\n                    <jats:italic>et al<\/jats:italic>\n                    engineered the V\u03b41 subset of \u03b3\u03b4 T cells with a CAR targeting prostate stem cell antigen (PSCA) and compared these cells to CAR-engineered V\u03b42 \u03b3\u03b4 and conventional \u03b1\u03b2 T cells in preclinical pancreatic cancer models. All three groups showed comparable tumor killing efficacy, but the CAR V\u03b41 T cells induced none of the GvHD or systemic toxicity seen with CAR \u03b1\u03b2 T cells. They also displayed lower exhaustion than CAR V\u03b42 cells, suggesting potential for greater persistence. V\u03b41 CAR T cells could be expanded robustly ex vivo and remained highly potent even after cryopreservation, a key \u201coff-the-shelf\u201d requirement. These findings position CAR V\u03b41 T cells as a safer alternative to traditional CAR T cells. Future rigorous clinical evaluation will be needed to confirm superior safety and efficacy of this promising approach in patients.\n                  <\/jats:p>","DOI":"10.1136\/jitc-2025-014088","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T14:15:14Z","timestamp":1778249714000},"page":"e014088","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["PSCA CAR V\u03b41 T cells: a safer off-the-shelf CAR T therapy for pancreatic cancer?"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-8993","authenticated-orcid":false,"given":"Joseph A","family":"Fraietta","sequence":"first","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6089-9992","authenticated-orcid":false,"given":"Jason J","family":"Lohmueller","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Center for Systems Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"2026050807150457000_14.5.e014088.1","doi-asserted-by":"crossref","first-page":"e530","DOI":"10.1097\/MPA.0000000000002489","article-title":"Factors Driving Pancreatic Cancer Survival Rates","volume":"54","author":"Rahib","year":"2025","journal-title":"Pancreas"},{"key":"2026050807150457000_14.5.e014088.2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1706169"},{"key":"2026050807150457000_14.5.e014088.3","doi-asserted-by":"crossref","DOI":"10.1186\/s40164-025-00654-3","article-title":"Addressing graft-versus-host disease in allogeneic cell-based immunotherapy for cancer","volume":"14","author":"Lyu","year":"2025","journal-title":"Exp Hematol Oncol"},{"key":"2026050807150457000_14.5.e014088.4","doi-asserted-by":"crossref","first-page":"152411","DOI":"10.1016\/j.seminoncol.2025.152411","article-title":"Tumor tough, therapy smarter: Rethinking CAR-T for pancreatic cancer","volume":"52","author":"Guirguis","year":"2025","journal-title":"Semin Oncol"},{"key":"2026050807150457000_14.5.e014088.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00722-1"},{"key":"2026050807150457000_14.5.e014088.6","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-023-01653-8","article-title":"\u03b3\u03b4 T cells: origin and fate, subsets, diseases and immunotherapy","volume":"8","author":"Hu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"2026050807150457000_14.5.e014088.7","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-011890","article-title":"Comparative efficacy and safety of PSCA CAR-engineered V\u03b41 \u03b3\u03b4 T cells for immunotherapy of pancreatic cancer","volume":"13","author":"Li","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026050807150457000_14.5.e014088.8","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.763773","article-title":"Bone Marrow-Resident V\u03b41 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma","volume":"8","author":"Brauneck","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"2026050807150457000_14.5.e014088.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01448-7"},{"key":"2026050807150457000_14.5.e014088.10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800636R"}],"container-title":["Journal for ImmunoTherapy of 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