Uckun F M, Myers D E, Irvin J D, Kuebelbeck V M, Finnegan D, Chelstrom L M, Houston L L
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis.
Leuk Lymphoma. 1993 Apr;9(6):459-76. doi: 10.3109/10428199309145753.
We have successfully constructed highly potent and selective anti-CD19 PAP immunotoxins using each of the three crosslinking agents, SPDP, LC-SPDP, or SMPT, to generate an intermolecular bridge between the B43 MoAb and PAP toxin moieties. These immunotoxins were selectively immunoreactive with and cytotoxic against CD19+ B-lineage ALL cells. In this report, we compared (a) in vivo chemical, immunological, and biological stability, (b) in vivo immunogenicity, and (c) in vivo anti-leukemic activity of various B43-PAP immunotoxin constructs. Our data recommend the use of SPDP and SMPT rather than LC-SPDP for generation of B43(anti-CD19)-PAP immunotoxins as clinical anti-leukemic agents. To our knowledge, this is the first comparative analysis of the in vivo pharmacokinetic features, immunogenicity, and anti-leukemic activity of anti-CD19 PAP immunotoxins that were prepared with different heterobifunctional crosslinking agents.
我们已成功构建了高效且具选择性的抗 CD19 PAP 免疫毒素，使用三种交联剂（SPDP、LC-SPDP 或 SMPT）中的每一种，在 B43 单克隆抗体和 PAP 毒素部分之间生成分子间桥。这些免疫毒素对 CD19 + B 系急性淋巴细胞白血病细胞具有选择性免疫反应性和细胞毒性。在本报告中，我们比较了各种 B43-PAP 免疫毒素构建体的（a）体内化学、免疫和生物学稳定性，（b）体内免疫原性，以及（c）体内抗白血病活性。我们的数据建议使用 SPDP 和 SMPT 而非 LC-SPDP 来生成 B43（抗 CD19）-PAP 免疫毒素作为临床抗白血病药物。据我们所知，这是首次对用不同异双功能交联剂制备的抗 CD19 PAP 免疫毒素的体内药代动力学特征、免疫原性和抗白血病活性进行比较分析。
