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Therapeutic Use of Anti-CD22 Antibodies for Inducing Trogocytosis

机译:抗CD22抗体诱导轮状细胞增多症的治疗用途

摘要

Disclosed are methods and compositions of anti-B cell antibodies, preferably anti-CD22 antibodies, for diagnosis, prognosis and therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. In certain embodiments, trogocytosis induced by anti-B cell antibodies may determine antibody efficacy, disease responsiveness and prognosis of therapeutic intervention. In other embodiments, optimal dosages of therapeutic antibody may be selected by monitoring the degree of trogocytosis induced by anti-B cell antibodies. Other characteristics of anti-B-cell antibodies that may be monitored include inducing phosphorylation of CD22, CD79a and CD79b; inducing translocation of CD22, CD79a and CD79b to lipid rafts; inducing caspase-dependent apoptosis; increasing pLyn, pERKs and pJNKs; decreasing constitutively-active p38; or inducing mitochondrial membrane depolarization, generation of reactive oxygen species, upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-xl, Mcl-1 and Bcl-2.
机译:公开了用于B细胞相关疾病例如B细胞恶性肿瘤,自身免疫疾病和免疫功能障碍疾病的诊断,预后和治疗的抗B细胞抗体,优选抗CD22抗体的方法和组合物。在某些实施方案中,由抗B细胞抗体诱导的吞噬作用可以确定抗体功效,疾病反应性和治疗干预的预后。在其他实施方案中,可以通过监测由抗B细胞抗体诱导的吞噬作用的程度来选择治疗性抗体的最佳剂量。可以监测的抗B细胞抗体的其他特征包括诱导CD22,CD79a和CD79b的磷酸化;诱导CD22,CD79a和CD79b易位至脂质筏;诱导胱天蛋白酶依赖性细胞凋亡;增加pLyn,pERK和pJNK;降低组成型活性p38;或诱导线粒体膜去极化,产生活性氧,上调凋亡前Bax和下调抗凋亡Bcl-xl,Mcl-1和Bcl-2。

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