{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:55:00Z","timestamp":1791266100423,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Cancer immunotherapy with immune checkpoint inhibitors (ICIs), i.e., antibodies targeting inhibitory ICs, such as PD-1, PD-L1, and CTLA-4, have successfully revolutionized cancer treatment. One of the most promising cancer immunotherapies is based on bi-specific T-cell engagers that simultaneously bind with one arm to a tumor-associated antigen on tumor cells and with the other one to the CD3 complex on T cells to form a TCR-MHC-independent immune synapse. We previously generated four novel tribodies, tri-specific antibody derivative constructs, made up of a Fab targeting 5T4, an oncofetal tumor antigen expressed on several types of tumors, an scFv targeting CD3 on T cells, and an additional scFv specific for an immune checkpoint. In particular, the 53L10 tribody, targeting PD-L1, displayed the best binding properties and stronger anti-tumor activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    in mouse models. Here, we further investigated the anti-tumor potential of 53L10 by testing its effects on a panel of tumor cell types with a more aggressive profile, including gastric, pancreatic, prostate, ovarian, and epidermoid tumor cells. We found that 53L10 was very effective on these cells by inducing stronger T-cell activation and tumor cell lysis than the parental bi-specific 53P lacking an ICI. To further test its therapeutic potential, we also analyzed its stability and the effects on tumor T-cell infiltration\n                    <jats:italic>in vivo<\/jats:italic>\n                    on a mouse model. 53L10 was found to be stable after incubation in serum at 37\u00a0\u00b0C for 3 days and induced a more efficient and earlier increase in tumor tissues of both CD4 and CD8 T cells than the parental bi-specific 53P. These findings support further preclinical evaluation of 53L10 as a new tool for multiple solid tumor-targeted therapeutic approaches.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1934039","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:32Z","timestamp":1791264092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["53L10 T-cell engager tribody for immunotherapy of multiple solid tumors"],"prefix":"10.3389","volume":"17","author":[{"given":"Margherita","family":"Passariello","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies, University of Naples \u201cFederico II\u201d","place":["Naples, Italy"]},{"name":"Ceinge-Biotecnologie Avanzate s.c.a.r.l.","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Belardo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies, University of Naples \u201cFederico II\u201d","place":["Naples, Italy"]},{"name":"Ceinge-Biotecnologie Avanzate s.c.a.r.l.","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Inoue","sequence":"additional","affiliation":[{"name":"Chiome Bioscience Inc.","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Kajiwara","sequence":"additional","affiliation":[{"name":"Chiome Bioscience Inc.","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Rapuano Lembo","sequence":"additional","affiliation":[{"name":"Ceinge-Biotecnologie Avanzate s.c.a.r.l.","place":["Naples, Italy"]},{"name":"European School of Molecular Medicine, 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