{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:59:35Z","timestamp":1787169575964,"version":"build-2736575974"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanofi","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["5R01AI164744"],"award-info":[{"award-number":["5R01AI164744"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,22]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitors have transformed cancer therapy, yet many patients fail to achieve durable responses due to insufficient T cell reinvigoration. Cytokines offer promise for enhancing immunotherapy, but their clinical use is limited by toxicity and a narrow therapeutic index. Immunocytokines, engineered fusion proteins combining antibody specificity with cytokine activity, aim to overcome these challenges by targeting cytokine delivery to immune cells or the tumor microenvironment. We describe SAR445877 (SAR\u2019877), a potentially novel PD-1\u2013targeted immunocytokine that fuses a high-affinity anti\u2013PD-1 antibody with a detuned IL-15\/IL-15R\u03b1 sushi domain complex. SAR\u2019877 blocks PD-1\/PD-L1 and PD-1\/PD-L2 interactions while selectively delivering IL-15 signals to PD-1\n                    <jats:sup>+<\/jats:sup>\n                    T cells, enhancing proliferation and activation of antigen-experienced CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and NK cells, while minimizing systemic inflammation. Mechanistically, SAR\u2019877 activates STAT5 signaling in PD-1\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes and restores effector function in exhausted T cells. In preclinical models, a murine surrogate of SAR\u2019877 accelerated viral clearance and induced robust antitumor immunity by expanding cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and promoting Th1 polarization. Notably, SAR\u2019877 outperformed anti\u2013PD-1 plus untargeted IL-15, highlighting the therapeutic potential of targeted IL-15 delivery. These findings position SAR\u2019877 as a promising next-generation immunotherapy with enhanced efficacy and reduced cytokine-associated toxicities.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.198701","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:00:14Z","timestamp":1777564814000},"source":"Crossref","is-referenced-by-count":2,"title":["PD-1\u2013targeted IL-15 mutein activates CD8+ and CD4+ T cells in infection and cancer"],"prefix":"10.1172","volume":"11","author":[{"given":"Isaraphorn","family":"Pratumchai","sequence":"first","affiliation":[{"name":"The Scripps Research Institute, Department of Immunology and Microbiology, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, Massachusetts, 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