{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T19:37:32Z","timestamp":1770925052663,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Shanghai Sailing Program","award":["24YF2715300"],"award-info":[{"award-number":["24YF2715300"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibody-dependent cellular cytotoxicity is a key mechanism for antibody-based therapeutics, and current engineering strategies to enhance ADCC primarily rely on two approaches: Fc mutations to improve the antibody\u2019s intrinsic CD16a affinity, or the fusion of binding-modules targeting NK cell receptors. The former often compromises antibody stability and induces CD16a downregulation; the latter occupies sites critical for target association and limits the assembly of multi-specific therapeutics. Here, we introduce a novel Fc engineering approach wherein the CH2 domain of the Fc region is replaced with an anti-NKp46 VHH named VIF-Ig. It has been reported that NKp46 expression remains unaltered after NK cell activation across various tumor microenvironments, addressing a key limitation of CD16a-dependent strategies. The novel molecules exhibit potent ADCC, high thermal stability, and retain FcRn binding for favorable pharmacokinetic profiles. Furthermore, we demonstrate that VIF-Ig can accommodate VHHs to target various epitopes. Thus, this versatile modular platform is suitable for developing next-generation NK cell or even other cell engagers with enhanced efficacy and tunable specificity, especially for emerging multi-specific immune cell engagers.<\/jats:p>","DOI":"10.1093\/protein\/gzag003","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T12:42:56Z","timestamp":1769172176000},"source":"Crossref","is-referenced-by-count":0,"title":["VIF-Ig: a novel fc framework for ADCC by incorporation of VHH unit"],"prefix":"10.1093","volume":"39","author":[{"given":"Yaohui","family":"Li","sequence":"first","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichen","family":"Huang","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]},{"name":"Research Center for Advanced Science and Technology , The University of Tokyo, Meguro, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingdan","family":"Duan","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]},{"name":"VelaVigo (Shanghai) Limited , Pudong district 200131,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Zhao","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiefu","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory , No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Jing","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kebing","family":"Yu","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Chuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4322-2127","authenticated-orcid":false,"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Fuhong Biotherapeutics , Protein Sciences and Pharmacology, Shanghai, Pudong district 200120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"2026021213561262200_ref1","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1080\/19420862.2015.1008353","article-title":"The neonatal fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity","volume":"7","author":"Abdiche","year":"2015","journal-title":"mAbs"},{"key":"2026021213561262200_ref2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/978-1-0716-4591-8_18","volume-title":"Epitope Mapping 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