Okabe T, Kaizu T, Fujisawa M, Watanabe J, Takaku F
Jpn J Med. 1985 Aug;24(3):250-6. doi: 10.2169/internalmedicine1962.24.250.
Monoclonal antibodies to small cell lung cancer (SCLC) were produced by fusion of P3X63/AgU1 mouse myeloma cells with spleen cells from BALB/c mice immunized against intact cells of SCLC tumors grown in BALB/c athymic nude mice. The antibody TFS-2 demonstrated "pancarcinoma" reactivity showing binding to non-small cell lung cancer (NSCLC) and carcinomas derived from other organs such as stomach, pancreas, and colon. This antibody failed to react with a variety of normal tissues including lung, bone marrow, spleen, stomach, colon, and pancreas. TFS-2 showed complement-mediated cytolysis of target cells. TFS-2 had no significant effects on hematopoietic stem cells. This antibody will serve as a powerful tool for the in vitro removal of tumor cells from bone marrow, thus facilitating high-dose chemotherapy of SCLC with autologous bone marrow transplantation. In contrast, TFS-4 monoclonal antibody reacted specifically with SCLC but not with NSCLS tumors. This antibody can distinguish SCLC from NSCLC tumors in histologic diagnosis at transbronchial biopsy, and in cytological identification of tumor cells in malignant effusion, and in infiltrated bone marrow. Radiolabeled TSF-4 specifically accumulated into SCLC tumors that were implanted subcutaneously into athymic nude mice. Thus, the antibody will be useful not only for diagnosis of lung cancer but also for targeting anti-tumor agents.
通过将P3X63/AgU1小鼠骨髓瘤细胞与来自用在BALB/c无胸腺裸鼠体内生长的小细胞肺癌(SCLC)肿瘤完整细胞免疫的BALB/c小鼠的脾细胞融合,制备了针对小细胞肺癌的单克隆抗体。抗体TFS-2表现出“泛癌”反应性,与非小细胞肺癌(NSCLC)以及源自其他器官如胃、胰腺和结肠的癌发生结合。该抗体未能与包括肺、骨髓、脾、胃、结肠和胰腺在内的多种正常组织发生反应。TFS-2显示出补体介导的靶细胞细胞溶解作用。TFS-2对造血干细胞没有显著影响。该抗体将成为从骨髓中体外清除肿瘤细胞的有力工具,从而促进小细胞肺癌自体骨髓移植的高剂量化疗。相比之下,TFS-4单克隆抗体与小细胞肺癌特异性反应,但与非小细胞肺癌肿瘤无反应。该抗体可在经支气管活检的组织学诊断、恶性胸腔积液中肿瘤细胞的细胞学鉴定以及浸润骨髓中区分小细胞肺癌与非小细胞肺癌肿瘤。放射性标记的TSF-4特异性积聚到皮下植入无胸腺裸鼠体内的小细胞肺癌肿瘤中。因此,该抗体不仅可用于肺癌诊断,还可用于靶向抗肿瘤药物。