{"doi":"10.1101/2022.05.29.493918","title":"Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection","abstract":"Summary Low dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due to the cytokine’s preferential expansion of immunosuppressive regulatory T cells (T Reg s). However, high toxicity, short serum half-life, and off-target immune cell activation limit the clinical potential of IL-2 treatment. Recent work showed that complexes comprising hIL-2 and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating T Reg s over immune effector cells. Although promising, therapeutic translation of this approach is complicated by the need to optimize dosing ratios and by the instability of the cytokine/antibody complex. We leveraged structural insights to engineer a single-chain hIL-2/F5111 antibody fusion protein, termed F5111 immunocytokine (IC), that potently and selectively activates and expands T Reg s. F5111 IC conferred protection in mouse models of colitis and checkpoint inhibitor-induced diabetes mellitus. These results provide a roadmap for IC design and establish a T Reg -biased immunotherapy that could be clinically translated for autoimmune disease treatment.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303423,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":388904,"name":"Marcos Iglesias","orcid":"0000-0002-7523-5950","position":1,"is_corresponding":false},{"id":868917,"name":"Jakub Tomala","orcid":"0000-0002-6315-2832","position":2,"is_corresponding":false},{"id":235280,"name":"Arabella Young","orcid":"0000-0002-6845-9753","position":3,"is_corresponding":false},{"id":235279,"name":"Jennifer Smith","orcid":"0000-0002-5662-1776","position":4,"is_corresponding":false},{"id":563909,"name":"Joseph A. Perry","orcid":null,"position":5,"is_corresponding":false},{"id":869423,"name":"Edward Gebara","orcid":null,"position":6,"is_corresponding":false},{"id":868918,"name":"Amy Cross","orcid":"0000-0002-2592-6251","position":7,"is_corresponding":false},{"id":563093,"name":"Laurene S. Cheung","orcid":"0000-0002-5759-9742","position":8,"is_corresponding":false},{"id":615681,"name":"Arbor G. Dykema","orcid":"0000-0001-5835-3261","position":9,"is_corresponding":false},{"id":568625,"name":"Brian Orcutt-Jahns","orcid":"0000-0002-1436-1224","position":10,"is_corresponding":false},{"id":869424,"name":"Tereza Henclová","orcid":null,"position":11,"is_corresponding":false},{"id":869425,"name":"Jaroslav Goliáš","orcid":null,"position":12,"is_corresponding":false},{"id":868919,"name":"Jared Balolong","orcid":"0000-0003-4119-2822","position":13,"is_corresponding":false},{"id":868920,"name":"Luke M. Tomasovic","orcid":"0000-0002-1459-3252","position":14,"is_corresponding":false},{"id":868921,"name":"David P. Funda","orcid":"0000-0001-8327-6931","position":15,"is_corresponding":false},{"id":405318,"name":"Aaron S. Meyer","orcid":"0000-0003-4513-1840","position":16,"is_corresponding":false},{"id":59439,"name":"Drew M. Pardoll","orcid":"0000-0001-6215-1013","position":17,"is_corresponding":false},{"id":868922,"name":"Joanna Hester","orcid":"0000-0002-7466-3849","position":18,"is_corresponding":false},{"id":834103,"name":"Fadi Issa","orcid":"0000-0002-8279-7732","position":19,"is_corresponding":false},{"id":305888,"name":"Christopher A. Hunter","orcid":"0000-0003-3092-1428","position":20,"is_corresponding":false},{"id":235418,"name":"Mark S. Anderson","orcid":"0000-0002-3093-4758","position":21,"is_corresponding":false},{"id":7899,"name":"Jeffrey A. 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