MONOCLONAL ANTIBODIES TO SMALL CELL CARCINOMA OF THE LUN

我们已经生产了四种可能有用的单克隆抗体 （MoAb）似乎对小细胞癌具有相对特异性， 肺（SCCL）。 这四种单克隆抗体，沿着其他鼠和人单克隆抗体， 我们建议开发的，将用于研究免疫生物学， SCCL细胞，从而为潜在的免疫治疗奠定基础。 在自体骨髓移植项目中治疗这种疾病。 新鲜 从具有SCCL细胞系的患者中分离的肿瘤细胞， 达特茅斯医学院将用于各种体外研究， 以及产生另外的杂交瘤。 新鲜的反应性 将通过以下方式评估分离的SCCL组织和细胞系 细胞荧光造影和补体依赖性细胞毒性。 细胞表面 SCCL细胞的特征性抗原将被部分纯化， 其特征在于并用于制备第二代 抗SCCL单克隆抗体。SCCL中抗原表达的异质性 在来自患者的单个细胞群中，以及SCCL细胞系和 SCCL细胞系的克隆将通过细胞荧光照相术进行评价。 测定 为了检测患者体液中的SCCL相关抗原， 开发并用于将细胞系的抗原表达与 ACCL患者的血清与疾病参数。 单克隆抗体诱导 细胞表面抗原的调节或肿瘤细胞的选择将是 被评估为可能的肿瘤细胞逃逸机制。 将尝试 开发一组能够消除肿瘤细胞的单克隆抗体， 逃跑 总的来说，这些研究代表了一种全面的方法， 单克隆抗体在诊断和治疗中的潜在应用评价 和SCCL细胞生物学的基础研究。 （IB）

We have already produccd four potentially useful monoclonal antibodies (MoAbs) that appear to be relatively specific for small cell carcinoma of the lung (SCCL). These four MoAbs, along with other murine and human MoAbs that we propose to develop, will be utilized to study the immunobiology of SCCL cells and thus to deveIop the basis for potential immunotherapy of this disease in an autologous bone marrow transplantation program. Freshly isolated tumor cells from patients with SCCL cell lines available at the Dartmouth Medical School will be used in a variety of in vitro studies as well as the production of additional hybridomas. Reactivities with freshly isolated SCCL tissue as well as cell lines will be assessed by cytofluorography and by complement-dependent cytotoxicity. Cell surface antigens characteristic of SCCL cells will be purified, partially characterized and used for the preparation of a second generation of anti-SCCL MoAbs. Heterogeneity of antigen expression in SCCL within and among individual cell populations from patients, and SCCL cell lines and clones of SCCL cell lines will be evaluated by cytofluorography. Assays for detection of SCCL-associated antigens in body fluids of patients will be developed and used to correlate antigen expression by cell lines and in the serum of patients with ACCL with disease parameters. MoAb induced modulation of cell surface antigens or tumor cell selection will be evaluated as possible tumor cell escape mechanisms. Attempts will be made to develop a panel of MoAbs that is capable of abrogating tumor cell escape. Overall, these studies represent a comprehensive approach to an evaluation of the potential utility of MoAbs in the diagnosis and therapy of SCCL and in basic studies of SCCL cell biology. (IB)