Chicken-derived CD20 antibodies with potent B-cell depletion activity.
Chicken-derived CD20 antibodies with potent B-cell depletion activity.
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DOI：
10.1111/bjh.18438
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发表时间：
2022-11
影响因子：
6.5
通讯作者：
中科院分区：
文献类型：
--
作者：
我们报道了四种新的抗人类CD20 （hCD20）单克隆抗体（mab），这些抗体是从一个系统发育上遥远的物种-鸡中发现的。与临床使用的小鼠-人嵌合抗hcd20抗体利妥昔单抗相比，鸡-人嵌合抗体的抗体依赖性细胞毒性（ADCC）增强≥10倍，补体依赖性细胞毒性（CDC）增强4 - 8倍。因此，据我们所知，这些单抗是第一个在fc介导的作用机制上明显优于利妥昔单抗的单抗。与利妥昔单抗相比，该抗体对健康人全血中B细胞的杀伤能力强20 - 100倍，并在体内保持药效。其中一种单克隆抗体AC1可以结合小鼠CD20，表明其特异性为当前（小鼠来源的）抗hCD20单克隆抗体无法获得的新的hCD20表位。一种人源化的抗体hAC11-10，通过互补决定区（CDR）嫁接到人可变区框架中，该分子保留了ADCC，体外人全血B细胞消耗和体内亲本淋巴瘤细胞消耗的活性。这些单克隆抗体代表了有希望的单一治疗候选药物，可以改善目前淋巴细胞恶性肿瘤不太理想的临床结果，并为开发下一代cd20介导的免疫疗法提供了生物学相关分子库，包括双特异性T细胞接合物（BiTE）、抗体-药物偶联物（ADC）和嵌合抗原受体工程T细胞（CAR-T）细胞。
We report four novel anti-human CD20 (hCD20) monoclonal antibodies (mAbs) discovered from a phylogenetically distant species – chickens. The chicken-human chimeric antibodies exhibit ≥10-fold enhanced antibody-dependent cellular cytotoxicity (ADCC) and 4–8-fold stronger complement-dependent cytotoxicity (CDC) relative to the clinically used mouse-human chimeric anti-hCD20 antibody Rituximab. Thus, to our knowledge these mAbs are the first to significantly outperform Rituximab in both Fc-mediated mechanisms of action. The antibodies show 20–100-fold superior depletion of B cells in whole blood from healthy humans relative to Rituximab and retain efficacy in vivo. One of the mAbs, AC1, can bind mouse CD20, indicating specificity for a novel hCD20 epitope inaccessible to current (mouse-derived) anti-hCD20 mAbs. A humanized version of one antibody, hAC11-10, was created by complementarity-determining region (CDR) grafting into a human variable region framework and this molecule retained the ADCC, in vitro human whole-blood B cell depletion, and in vivo lymphoma cell depletion activities of the parent. These mAbs represent promising monotherapy candidates for improving upon current less-than-ideal clinical outcomes in lymphoid malignancies and provide an arsenal of biologically relevant molecules for the development of next-generation CD20-mediated immunotherapies including bispecific T cell engagers (BiTE), antibody-drug conjugates (ADC) and chimeric antigen receptor-engineered T (CAR-T) cells.
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影响因子：
6.2
作者：
Grant, Barbara W.;Jung, Sin-Ho;Johnson, Jeffrey L.;Kostakoglu, Lale;Hsi, Eric;Byrd, John C.;Jones, Jeffrey;Leonard, John P.;Martin, S. Eric;Cheson, Bruce D.
通讯作者：
Cheson, Bruce D.
影响因子：
28.5
作者：
Breton CS;Nahimana A;Aubry D;Macoin J;Moretti P;Bertschinger M;Hou S;Duchosal MA;Back J
通讯作者：
Back J
DOI：
10.3324/haematol.2011.047159
发表时间：
2011-12-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Boross, Peter;Jansen, J. H. Marco;Leusen, Jeanette H. W.
通讯作者：
Leusen, Jeanette H. W.
影响因子：
6.5
作者：
Awasthi, Aradhana;Ayello, Janet;Cairo, Mitchell S.
通讯作者：
Cairo, Mitchell S.
影响因子：
20.3
作者：
Beers, Stephen A.;French, Ruth R.;Cragg, Mark S.
通讯作者：
Cragg, Mark S.