{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:41:03Z","timestamp":1790516463584,"version":"4.1.0"},"reference-count":25,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hemophilia A is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene (F8). Treatment with recombinant or plasma-derived FVIII replacement therapy is standard therapy. A major problem in treating hemophilia A patients with therapeutic FVIII is that 20% to 30% of these patients produce neutralizing anti-FVIII antibodies (inhibitors) because they are not immunologically tolerant to this human protein. Hence, there is a need to establish tolerogenic protocols to FVIII epitopes. To specifically target FVIII-specific B cells, we engineered immunodominant FVIII domains (A2 and C2) as a chimeric antigen receptor expressed by both human and murine cytotoxic T cells. This FVIII domain engineered B-cell antibody receptor (BAR) that expresses T cells was capable of killing FVIII-reactive B-cell hybridomas in vitro and in vivo. Moreover, FVIII BAR CD8 T cells blocked the development of specific antibody from unimmunized spleen cells stimulated polyclonally with lipopolysaccharide in vitro. In addition, adoptive transfer of FVIII A2- and C2-BAR CD8 T cells significantly reduced the anti-FVIII antibody formation in hemophilic mice. These data suggest that BAR-engineered T cells are a promising approach for future prophylactic treatment for patients with severe hemophilia A who are at high risk of developing inhibitors.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018018556","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T11:47:17Z","timestamp":1537357637000},"page":"2332-2340","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":55,"title":["Engineered FVIII-expressing cytotoxic T cells target and kill FVIII-specific B cells in vitro and in vivo"],"prefix":"10.1182","volume":"2","author":[{"given":"Kalpana","family":"Parvathaneni","sequence":"first","affiliation":[{"name":"Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4918-2610","authenticated-orcid":false,"given":"David W.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2018,9,19]]},"reference":[{"issue":"22","key":"2020021108363376800_B1","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1182\/blood-2013-01-478669","article-title":"Progress toward inducing immunologic tolerance to factor VIII","volume":"121","author":"Scott","year":"2013","journal-title":"Blood"},{"key":"2020021108363376800_B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cellimm.2015.10.010","article-title":"Why do immunology research in hemophilia?","volume":"301","author":"Scott","year":"2016","journal-title":"Cell Immunol"},{"issue":"12","key":"2020021108363376800_B3","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1182\/blood-2011-09-379453","article-title":"F8 gene mutation type 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