{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:54:45Z","timestamp":1793426085643,"version":"4.5.0"},"reference-count":78,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,12]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>We report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised &amp;gt;94% of the total lymphocytes in 4 of 5 patients. Tumor responses were observed in 4 of 5 patients with 3 complete responses, 1 mixed response, and 1 patient whose disease progressed rapidly and with relative loss of CD37 expression. Three patients experienced prolonged and severe pancytopenia, and in 2 of these patients, efforts to ablate CAR-37 T cells, which were engineered to coexpress truncated epidermal growth factor receptor, with cetuximab were unsuccessful. Hematopoiesis was restored in these 2 patients after allogeneic hematopoietic stem cell transplantation. No other severe, nonhematopoietic toxicities occurred. We investigated the mechanisms of profound pancytopenia and did not observe activation of CAR-37 T cells in response to hematopoietic stem cells in\u00a0vitro or hematotoxicity in humanized models. Patients with pancytopenia had sustained high levels of interleukin-18 (IL-18) with low levels of IL-18 binding protein in their peripheral blood. IL-18 levels were significantly higher in CAR-37\u2013treated patients than in both cytopenic and noncytopenic cohorts of CAR-19\u2013treated patients. In conclusion, CAR-37 T cells exhibited antitumor activity, with significant CAR expansion and cytokine production. CAR-37 T\u00a0cells may be an effective therapy in hematologic malignancies as a bridge to hematopoietic stem cell transplant. This trial was registered at www.ClinicalTrials.gov as #NCT04136275.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024104","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T16:08:49Z","timestamp":1716480529000},"page":"1153-1167","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":39,"title":["Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies"],"prefix":"10.1182","volume":"144","author":[{"given":"Matthew J.","family":"Frigault","sequence":"first","affiliation":[{"name":"1Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, MA"},{"name":"2Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA"},{"name":"3Department of Pathology and Department of Medicine, Harvard Medical School, Boston, 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