Bejcek B E, Wang D, Berven E, Pennell C A, Peiper S C, Poppema S, Uckun F M, Kersey J H
Bone Marrow Transplant Program, University of Minnesota, Minneapolis 55455, USA.
Cancer Res. 1995 Jun 1;55(11):2346-51.
Antibodies that recognize antigens restricted to leukemia, lymphoma, and normal hematopoietic cells represent a unique opportunity to develop therapeutics, because they have the potential for relatively selective treatment of these diseases. Antibodies that recognize the CD19 antigen found on normal and malignant B cells, but not on stem cells, have been used to develop immunoconjugates. However, these conjugates are large and might be suboptimal in tumor penetration when compared to molecules using smaller single chain Fv (scFv) antibody fragments. scFv has the advantage of being a molecularly engineered homogeneous molecule. In this report, we demonstrate the cloning, expression, and binding of three anti-CD19 antibodies as scFvs. All three scFvs were successfully cloned and expressed. FVS191, derived from cell line B43, and FVS192, derived from SJ25C1, were properly refolded and bound CD19 antigen in FACS competition assays. These anti-CD19 scFv should be useful in the further development of diagnostic and therapeutic molecules.
识别局限于白血病、淋巴瘤及正常造血细胞的抗原的抗体，为开发治疗药物提供了独特契机，因为它们有对这些疾病进行相对选择性治疗的潜力。识别正常和恶性B细胞（而非干细胞）上发现的CD19抗原的抗体，已被用于开发免疫缀合物。然而，与使用较小单链Fv（scFv）抗体片段的分子相比，这些缀合物体积较大，在肿瘤渗透方面可能并非最佳。scFv具有分子工程化的同质分子的优势。在本报告中，我们展示了三种抗CD19抗体作为scFv的克隆、表达及结合情况。所有三种scFv均成功克隆并表达。源自细胞系B43的FVS191和源自SJ25C1的FVS192在FACS竞争试验中正确重折叠并结合CD19抗原。这些抗CD19 scFv应有助于诊断和治疗分子的进一步开发。
