抗CD22核糖核酸酶：制备与表征

Anti-CD22 Onconase: preparation and characterization.

作者信息

Newton Dianne L, Stockwin Luke H, Rybak Susanna M

机构信息

NCI-Frederick, National Institutes of Health, Frederick, MD, USA.

出版信息

Methods Mol Biol. 2009;525:425-43, xiv. doi: 10.1007/978-1-59745-554-1_22.

DOI:10.1007/978-1-59745-554-1_22

PMID:19252847

Abstract

Antibodies can be conjugated to effector molecules to derive targeted therapeutics with properties such as cell-specific cytotoxicity. The murine anti-CD22 antibody RFB4 linked to a member of the ribonuclease A superfamily, Onconase (Onc), becomes a potential drug candidate for non-Hodgkin's lymphoma. Onc is currently in Phase III clinical trials for unresectable malignant mesothelioma but conjugation to RFB4 considerably enhances its specificity for CD22+ lymphomas. RFB4-targeted Onc is effective in preclinical models, causes little non-specific toxicities in mice, and has favorable formulation properties. Derivatization and conjugation of RFB4 and Onc have been optimized.

摘要

抗体可与效应分子偶联，以获得具有细胞特异性细胞毒性等特性的靶向治疗药物。与核糖核酸酶A超家族成员Onconase（Onc）连接的鼠抗CD22抗体RFB4，成为非霍奇金淋巴瘤的潜在候选药物。Onc目前正处于不可切除恶性间皮瘤的III期临床试验阶段，但与RFB4偶联可大大提高其对CD22 +淋巴瘤的特异性。RFB4靶向的Onc在临床前模型中有效，在小鼠中几乎不引起非特异性毒性，并且具有良好的制剂特性。RFB4和Onc的衍生化和偶联已得到优化。