MONOCLONAL ANTIBODIES/SMALL CELL CARCINOMA OF THE LUNG

该项目旨在探索诊断和治疗 一组具有反应能力的单抗(MoAbbs)的潜能 与SCCL相关的或特定的细胞表面抗原。这个 大多数MoAbs是在本实验室制备的 这项正在进行的研究的第一年(现已进入第四年)和 此外，我们还获得了两个SCCL反应性MoAbTFS-2和TFS- 4这增强了我们进行我们提出的研究的能力。 特别是，我们将对SCCL进行前瞻性评估 以建立肿瘤免疫表型为目的有意义 临床相关性。所有肺癌患者都在 DHMC将对其肿瘤细胞进行免疫组织化学检查 用于表达由一组MoAbs定义的抗原。这个 DHMC肿瘤登记处将收集临床数据，从而 允许进行数据分析和关联。第二个项目将 正在开发一种灵敏的检测方法，用于检测微小的 其他细胞群中的SCCL细胞数量，如骨 骨髓。这将涉及多参数流式细胞术的使用 同时测定DNA含量和表面表达 SCCL 175。这项技术将被用来确定 并监测SCCL的疗效 自体骨髓移植中的骨髓净化 (ABMT)。另一个项目将研究MoAbs的潜力 使用免疫磁珠从骨髓中去除SCCL细胞。我们 将探索几种与磁性结合的MoAbs的用途 微球的能力，单独和组合，以 从无肿瘤的SCCL患者身上提取骨髓用于ABMT。最后， 我们将制备抗SCCL的杂合抗体(HA)和MoAbs 细胞毒效应细胞。这些医管局将接受检查，以确定其 调停SCCL致死的能力。我们希望这些临床前 立即将研究引向临床应用 患者的诊断和治疗。

This project is designed to explore the diagnostic and therapeutic potential of a panel of monoclonal antibodies (MoAbs) that react with SCCL-associated or specific cell surface antigens. The majority of the MoAbs were prepared in this laboratory during the first years of this on-going study (now in its 4th year) and in addition, we have acquired two SCCL-reactive MoAbs, TFS-2 and TFS- 4 that augment our ability to carry out the studies we propose. In particular, we will undertake a prospective evaluation of SCCL tumor immunophenotyping for the purpose of establishing meaningful clinical correlations. All patients with lung cancer seen at the DHMC will have their tumor cells examined by immunohistochemistry for the expression of antigens defined by a battery of MoAbs. The tumor registry of DHMC will collect the clinical data thus permitting data analyses and correlations. A second project will be the development of a sensitive test for the detection of small numbers of SCCL cells in other cell populations, such as bone marrow. This will involve the use of multiparameter flow cytometry to measure simultaneously DNA content and surface expression of SCCL 175. This technique will be used to establish the incidence of bone marrow metastases and to monitor the efficacy of SCCL purging of bone marrow for autologous bone marrow transplantation (ABMT). Another project will examine the potential of MoAbs to remove SCCL cells from bone marrow using immunomagnetic beads. We will explore the use of several MoAbs conjugated to magnetic microspheres for their abilities, alone and in combination, to prepare marrow from SCCL patients tumor-free for ABMT. Finally, we will prepare hetero-antibodies (HA) of anti-SCCL MoAbs and MoAbs to cytotoxic effector cells. These HA will be examined for their abilities to mediate SCCL killing. We expect these pre-clinical studies to lead immediately to clinical applications for the diagnosis and treatment of patients.