MONOCLONAL ANTIBODIES/SMALL CELL CARCINOMA OF THE LUNG

该项目旨在探索诊断和治疗 一组单克隆抗体（MoAb）的潜力， 与SCCL相关或特异性细胞表面抗原。 的 大多数单克隆抗体是在本实验室制备的， 这项正在进行的研究的第一年（现在是第四年）和 此外，我们还获得了两种SCCL反应性单克隆抗体，TFS-2和TFS-2。 4.增强我们进行我们提议的研究的能力。 特别是，我们将对SCCL进行前瞻性评估 肿瘤免疫表型，目的是建立有意义的 临床相关性 所有肺癌患者在 DHMC将通过免疫组织化学检查其肿瘤细胞 用于表达由一组单克隆抗体定义的抗原。 的 DHMC肿瘤登记处将收集临床数据， 允许数据分析和相关性。 第二个项目将 是一个敏感的检测小的发展 其他细胞群（如骨）中的SCCL细胞数量 骨髓。 这将涉及多参数流式细胞术的使用 同时测量DNA含量和表面表达， 第175章. 该技术将用于确定 的骨髓转移，并监测SCCL的疗效 自体骨髓移植骨髓净化 （ABMT）。 另一个项目将研究MoAb的潜力， 使用免疫磁珠从骨髓中去除SCCL细胞。 我们 将探索使用几种单克隆抗体结合到磁性 微球的能力，单独和组合， 从SCCL患者中制备无肿瘤的骨髓用于ABMT。 最后， 我们将制备抗SCCL单克隆抗体和单克隆抗体的异源抗体（HA）， 到细胞毒性效应细胞。 这些医管局将接受检查， 介导SCCL杀伤的能力。 我们希望这些临床前 研究，立即导致临床应用， 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.