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Immunol."],"abstract":"<jats:p>Biologic drugs, especially anti-TNF, are considered as the gold standard therapy in rheumatoid arthritis. However, non-uniform efficacy, incidence of infections, and high costs are major concerns. Novel tissue-specific agents may overcome the current limitations of systemic administration, providing improved potency, and safety. We developed a bispecific antibody (BsAb), combining human arthritic joint targeting, <jats:italic>via<\/jats:italic> the synovial-specific single-chain variable fragment (scFv)-A7 antibody, and TNF\u03b1 neutralization, <jats:italic>via<\/jats:italic> the scFv-anti-TNF\u03b1 of adalimumab, with the binding\/blocking capacity comparable to adalimumab -immunoglobulin G (IgG). Tissue-targeting capacity of the BsAb was confirmed on the human arthritic synovium <jats:italic>in vitro<\/jats:italic> and in a synovium xenograft Severe combined immune deficient (SCID) mouse model. Peak graft accumulation occurred at 48 h after injection with sustained levels over adalimumab-IgG for 7 days and increased therapeutic effect, efficiently decreasing tissue cellularity, and markers of inflammation with higher potency compared to the standard treatment. This study provides the first description of a BsAb capable of drug delivery, specifically to the disease tissue, and a strong evidence of improved therapeutic effect on the human arthritic synovium, with applications to other existing biologics.<\/jats:p>","DOI":"10.3389\/fimmu.2021.640070","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T23:33:01Z","timestamp":1613863981000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rheumatoid Arthritis"],"prefix":"10.3389","volume":"12","author":[{"given":"Mathieu","family":"Ferrari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimobi C.","family":"Onuoha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliane","family":"Fossati-Jimack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Nerviani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro L.","family":"Alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Pagani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Deantonio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Sblattero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Costantino","family":"Pitzalis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/nrrheum.2015.17","article-title":"Trojan horses and guided missiles: targeted therapies in the war on arthritis","volume":"11","author":"Ferrari","year":"2015","journal-title":"Nat Rev Rheumatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1093\/rheumatology\/kel253","article-title":"Mortality in rheumatoid arthritis. 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