{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T13:35:55Z","timestamp":1777642555643,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Nectin and nectin\u2010like proteins are cell adhesion molecules belonging to the immunoglobulin superfamily that also play a crucial role in the process of immune modulation by interacting with immune receptors like TIGIT, DNAM\u20101, CD96 and PVRIG. Nectin\u20104 is a tumour\u2010specific antigen that interacts exclusively with the inhibitory immune receptor TIGIT, resulting in inhibition of NK\u2010cell cytotoxicity and facilitating the process of immune evasion by the cancer cells in the tumour microenvironment. Therefore, deciphering the molecular and structural mechanisms underlying this novel interaction can provide insights for the development of targeted immunotherapeutic interventions. In this study, using structure\u2010guided mutagenesis studies, a novel TIGIT mutant is engineered exhibiting enhanced interaction affinity towards nectin\u20104 and reduced binding to other TIGIT ligands, such as PVR and nectin\u20102, which, in contrast to nectin\u20104, are predominantly expressed on healthy cells. Surface plasmon resonance\u2010based biophysical studies were done to characterize and compare the interaction kinetics of the wild\u2010type (WT) and the engineered mutant TIGIT ectodomains with their ligands. We have shown how a single point mutation of an amino acid residue located in the centre of the F strand of TIGIT dictates its interaction affinity with its ligand. These findings can provide a framework for the development of small\u2010sized non\u2010antibody therapeutics specifically targeted towards nectin\u20104 overexpressing cancer cells with minimal off\u2010target effects on healthy cells.<\/jats:p>","DOI":"10.1002\/eji.70179","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:55:46Z","timestamp":1775199346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2010Guided Engineering of TIGIT to Modulate Its Interaction With Nectin\u20104, a Tumour\u2010Specific Antigen for the Development of Therapeutic Strategy"],"prefix":"10.1002","volume":"56","author":[{"given":"Namrata","family":"Ganguli","sequence":"first","affiliation":[{"name":"Department of Bioscience and Biotechnology Indian Institute of Technology Kharagpur  Kharagpur 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