RADIOIMMUNOTHERAPY AND EXTRACORPOREAL ADSORPTION THERAPY STUDIES IN MACAQUES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究评估了放射性标记抗体治疗作为一种改善恶性血液病骨髓移植结果的方法。到目前为止，人类的大部分临床经验都是用碘标记的抗体和Y标记的抗体。虽然这种疗法最初的应答率很高，但大多数患者随后又复发了。我们的努力旨在通过去除未能到达靶组织并残留在血液中的导致非靶组织损伤的放射活动的比例，来提高这种治疗方法的疗效并减少其毒性。我们使用一种称为体外吸附疗法(ECAT)的过程。这包括通过将血液循环到含有捕获放射性分子的特殊材料的柱子中，然后将血液返回循环，从而去除循环中不与目标组织结合的抗体部分。我们的初步研究的目的是证明注射放射性标记抗体和ECAT程序可以安全进行，并且我们可以重现在其他地方观察到的结果。具体地说，我们试图证明，通过使用ECAT过滤系统，可以有效地清除血液中的游离放射性同位素。此外，我们的目标是表明，与正常组织相比，这一过程将提高辐射到靶细胞的比率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study evaluated radiolabeled antibody therapy as a means to improve the outcome of bone marrow transplantation for hematologic malignancies. The majority of the human clinical experience to date is with iodine-labeled and yttrium-labeled antibodies. Although the initial response rates to this therapy have been high, most patients subsequently relapse. Our efforts are aimed at improving the efficacy and diminishing the toxicity of this treatment modality by removing the proportion of radiation activity that fails to reach the target tissues and remains in the bloodstream, leading to non-target tissue damage. We use a process called extracorporeal adsorption therapy (ECAT). This consists of removing the portion of antibody that is in the circulation unbound to target tissues by cycling the blood into a column containing a special material that traps the radioactive molecules and then returns the blood back into the circulation. The objective of our pilot study is to demonstrate that the injection of radiolabeled antibody and the ECAT procedure could be performed safely, and that we could reproduce the results observed elsewhere. Specifically we seek to show that the blood can be effectively cleared of unbound radioisotope, by using the ECAT filtration system. Further, we aim to show that this procedure will improve the ratio of radiation delivered to target cells, as compared to normal tissues.