인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Hemophilia A (HA) is an X-linked recessive bleeding disorder in which patients are deficient in pro-coagulant factor VIII (FVIII) protein. Treatment of HA with regular infusions of FVIII is extremely effective, but 20-30% of patients will develop neutralizing antibodies to FVIII, called inhibitors. The development of inhibitors renders standard treatment ineffective and is a major impediment to therapy. Inhibitors are known to prefer epitopes on the C2 and A2 domains of FVIII, both critical for activity. One approach to tolerize patients to FVIII is to eliminate the population of B lymphocytes that recognize immunogenic epitopes on FVIII. Previous research has utilized cytotoxic T lymphocytes (CTLs) engineered to target FVIII-specific B lymphocytes with a chimeric antigen receptor displaying immunogenic domains of FVIII. As an alternative but related strategy, we have designed and produced a bispecific immunoconjugate to crosslink CTLs with FVIII-specific B lymphocytes. The immunoconjugate engages CTLs with an anti-CD8 arm, and displays the C2 domain of FVIII to attract FVIII-specific B lymphocytes. We hypothesize that contact between the two cell types will initiate CTL-mediated killing. Using C2-specific hybridomas as targets and blood-derived mixed human lymphocytes as a source of T cells, we have demonstrated via B-cell ELISpot assays that the construct is capable of initiating killing. We are continuing to explore the use of the immunoconjugate in tissue culture and are planning to conduct mouse experiments to examine its in vivo efficacy. Supported by NIH grant R21 HL152318 to DWS and JEW.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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