{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:50:44Z","timestamp":1791435044361,"version":"4.3.3"},"reference-count":68,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitors (ICI), such as antibodies against Programmed Death 1 (PD-1), are widely used to treat different types of cancer. Unfortunately, only a small subset of patients benefits from such treatments, and the systemic administration of ICIs can cause severe immune-related adverse events. To overcome these hurdles, we performed an\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    proof-of-concept investigation of recombinant adenoviral vectors encoding different variants of secreted PD-1 (sPD-1), differing in size, cysteine mutations, oligomerization, and effector functions. First, eight sPD-1 variants were screened, followed by the generation of recombinant adenoviruses with four of the highest-performing sPD-1 constructs based on qualitative analysis of sPD-1 secretion and ligand binding. The secretion of sPD-1 was analyzed using immunoblotting, while binding to PD-L1 and PD-L2 ligands was assessed using a pull-down assay and ELISA. In addition, the inhibition of PD-1:PD-L1 interaction was studied using cell-based signaling bioassays. It was demonstrated that the Fc-fusion sPD-1 variants resulted in the highest sPD-1 yields and were the most efficient in ligand binding. In particular, the single-chain Fc-fusion sPD-1 constructs were the most potent variants, as they effectively blocked PD-1-mediated signaling in T cells in two different coculture assays. The results of this\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    proof-of-concept study indicate that stable and well-secreted sPD-1 constructs have significant potential for site-specific immune gene therapy.\n                  <\/jats:p>","DOI":"10.1177\/10430342261422764","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T06:32:57Z","timestamp":1770877977000},"page":"733-743","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel, Stable, and Well-Secreted Single-Chain Fc Forms of Programmed Death-1 Immune Checkpoint Inhibitor Efficiently Block PD-1\/PD-L1 Interaction"],"prefix":"10.1177","volume":"37","author":[{"given":"Piia","family":"K\u00e4yhty","sequence":"first","affiliation":[{"name":"Ferring Ventures Oy, Kuopio, Finland"},{"name":"A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, 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Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics Laboratory and InFLAMES Research Flagship Center, Biochemistry, Faculty of Science and Engineering, \u00c5bo Akademi University, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna P.","family":"Lesch","sequence":"additional","affiliation":[{"name":"Ferring Ventures Oy, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo","family":"Yl\u00e4-Herttuala","sequence":"additional","affiliation":[{"name":"A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland"},{"name":"Heart Center, Kuopio University Hospital, Kuopio, Finland"},{"name":"Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari 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