Seon B K
Cancer Res. 1984 Jan;44(1):259-64.
In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of specific killing of human T-leukemia cells in vitro. These immunotoxins were prepared by conjugating ricin A chain (RIA) with our recently generated murine monoclonal antibodies, SN1 and SN2, the latter of which was obtained from a hybridoma clone N6/D11 described previously by Negoro and Seon (Cancer Res., 42: 4259-4262, 1982), directed to two unique human T-cell leukemia antigens. We have shown previously that these monoclonal antibodies do not react with non-T-leukemia cells nor with various normal cells including normal T-cells, thymocytes, and bone marrow cells (Proc. Natl. Acad. Sci. U. S. A., 80: 845, 1983; Cancer Res., 42: 4259, 1982). Control conjugate was also prepared by conjugating RIA with a murine monoclonal immunoglobulin G (IgG), the isotype of which is the same as that of SN1 and SN2, i.e., IgG1-kappa. In initial experiments, the cytotoxic activity of an SN1 IgG:RIA conjugate preparation and the control IgG conjugate preparation against leukemic T-cell lines and normal B-cell lines was tested by two different test procedures, i.e., by measuring direct killing of the cells and by measuring inhibitory activity against protein synthesis in the cells. In each test, the SN1 conjugate showed specific cytotoxic activity against T-leukemia cells, whereas the control conjugate was not cytotoxic against either T-leukemia cells or normal B-cells. Nearly complete killing of T-leukemia cells and inhibition of protein synthesis in T-leukemia cells were observed at the concentrations of 10(-8) to 10(-7) M of the SN1 IgG:RIA conjugate. In subsequent experiments, another preparation of SN1 IgG:RIA conjugate and an SN2 IgG:RIA conjugate preparation were tested individually and together for their inhibitory activity against protein synthesis in T-leukemia cells and control cells. With T-leukemia cells, specific inhibition was observed for both SN1 IgG:RIA and SN2 IgG:RIA. The combined use of these conjugates did not display a synergistic effect. Nevertheless, the combined use of different immunotoxins directed to different antigen molecules will be important in clinical use, since uncultured tumor cells derived freshly from patients, in general, display heterogeneity with respect to the expression of tumor-associated antigens. These immunotoxins may be useful for the in vitro eradication of tumor cells in the bone marrow taken from patients with T-cell leukemia.(ABSTRACT TRUNCATED AT 400 WORDS)
在本研究中，含单克隆抗人T细胞白血病抗体的免疫毒素在体外可特异性杀伤人类T白血病细胞。这些免疫毒素是通过将蓖麻毒蛋白A链（RIA）与我们最近制备的鼠单克隆抗体SN1和SN2偶联而成，其中SN2是从Negoro和Seon先前描述的杂交瘤克隆N6/D11（《癌症研究》，42: 4259 - 4262, 1982）获得的，针对两种独特的人类T细胞白血病抗原。我们先前已表明，这些单克隆抗体不与非T白血病细胞反应，也不与包括正常T细胞、胸腺细胞和骨髓细胞在内的各种正常细胞反应（《美国国家科学院院刊》，80: 845, 1983；《癌症研究》，42: 4259, 1982）。对照偶联物也是通过将RIA与鼠单克隆免疫球蛋白G（IgG）偶联制备的，其同种型与SN1和SN2相同，即IgG1 - κ。在初步实验中，通过两种不同的测试方法，即测量细胞的直接杀伤作用和测量对细胞内蛋白质合成的抑制活性，检测了SN1 IgG:RIA偶联物制剂和对照IgG偶联物制剂对白血病T细胞系和正常B细胞系的细胞毒性活性。在每次测试中，SN1偶联物对T白血病细胞显示出特异性细胞毒性活性，而对照偶联物对T白血病细胞或正常B细胞均无细胞毒性。在SN1 IgG:RIA偶联物浓度为10(-8)至10(-7) M时，观察到T白血病细胞几乎完全被杀伤以及T白血病细胞内蛋白质合成受到抑制。在随后的实验中，单独和共同测试了另一种SN1 IgG:RIA偶联物制剂和一种SN2 IgG:RIA偶联物制剂对T白血病细胞和对照细胞内蛋白质合成的抑制活性。对于T白血病细胞，SN1 IgG:RIA和SN2 IgG:RIA均观察到特异性抑制作用。这些偶联物的联合使用未显示出协同效应。然而，针对不同抗原分子的不同免疫毒素的联合使用在临床应用中将很重要，因为通常从患者新鲜获取的未培养肿瘤细胞在肿瘤相关抗原的表达方面表现出异质性。这些免疫毒素可能有助于在体外清除取自T细胞白血病患者的骨髓中的肿瘤细胞。（摘要截短至400字）
