Core B: Pharmaceutical Production

项目摘要/摘要--核心B 核心B，制药生产，负责生产单抗(MAb)， 该抗体结合有放射性核素α-211(~(211)At)和标记抗体~(211)At 共轭关系。Core将生产用于临床前研究的抗CD45和抗CD38单抗(项目1、2 3)制备临床级抗人CD45-BC8单抗和抗人CD38-OKT10单抗 临床试验(项目2和项目3)。单抗将与一种新的试剂(B10-NCS)偶联，以产生 ~(211)At标记~(211)At的单抗-B10结合物所有单抗和临床级试剂都将 在弗雷德·哈奇的生物制品生产设施(BPF)中进行生产、纯化和瓶装。B10-NCS 用于临床前研究的试剂和单抗-B10结合物将在适当的化学物质中生产 华盛顿大学的实验室。临床级BC8-B10结合物和OKT10-B10将 在弗雷德·哈奇的现行良好制造规范(CGMP)条件下生产、提纯和装瓶 最好的朋友。~(211)At的生产、分离和提纯将在威斯康星州医用回旋加速器设施和 威斯康星大学放射性核素生产实验室。用于临床前研究的211At-MAb-B10将在威斯康星州进行 放射化学实验室，以及临床试验中使用的211At-BC8-B10和211At-OKT10-B10 在威斯康星州大学的cGMP工厂。对生产的材料的测试将在威斯康星大学或弗雷德·哈奇进行，具体取决于 在化验上。从项目2和项目3获得的患者样本将被收集、处理和存储在 在项目1中使用的弗雷德·哈奇。

PROJECT SUMMARY / ABSTRACT – CORE B Core B, Pharmaceutical Production, is responsible for the production of the monoclonal antibodies (MAbs), the antibody conjugates, the alpha-emitting radionuclide astatine-211 (211At) and the 211At-labeled antibody conjugates. The Core will produce anti-CD45 and anti-CD38 MAbs used in preclinical studies (Projects 1, 2 and 3) and produce clinical grade anti-human CD45 BC8 MAb and anti-human CD38 OKT10 MAb used in clinical trials (Projects 2 and 3). The MAbs will be conjugated with a novel reagent (B10-NCS) to produce MAb-B10 conjugates for radiolabeling with astatine-211 (211At). All MAbs and clinical grade reagents will be produced, purified and vialed in the Biologics Production Facility (BPF) of the Fred Hutch. The B10-NCS reagent and MAb-B10 conjugates used for preclinical studies will be produced in appropriate chemical laboratories at the University of Washington. Clinical grade BC8-B10 conjugate and OKT10-B10 will be produced, purified and vialed under current good manufacturing practice (cGMP) conditions in the Fred Hutch BPF. Production, isolation and purification of the 211At will be done in the UW Medical Cyclotron Facility and UW Radionuclide Production Laboratory. The 211At-MAb-B10 for preclinical studies will be conducted in UW radiochemistry laboratory, and 211At-BC8-B10 and 211At-OKT10-B10 used in the clinical trials will be produced in a cGMP facility at UW. Testing of the materials produced will be conducted at UW or Fred Hutch, depending on the assay. Patient samples obtained from Projects 2 and 3 will be collected, processed and stored at the Fred Hutch for use in Project 1.