{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:22:15Z","timestamp":1789150935055,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T00:00:00Z","timestamp":1654905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["16695"],"award-info":[{"award-number":["16695"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3\u03b5 (CD1a x CD3\u03b5) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3\u03b5 induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3\u03b5 significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3\u03b5 is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease.<\/jats:p>","DOI":"10.3390\/cancers14122886","type":"journal-article","created":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T09:33:26Z","timestamp":1654940006000},"page":"2886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Novel Bispecific T-Cell Engager (CD1a x CD3\u03b5) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Caterina","family":"Riillo","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Caracciolo","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-5536","authenticated-orcid":false,"given":"Katia","family":"Grillone","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Poler\u00e0","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-2535","authenticated-orcid":false,"given":"Franca Maria","family":"Tuccillo","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori IRCCS-Fondazione G. 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