Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models.
Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models.
复制标题
特异性免疫毒素完全抑制人白血病细胞体内生长：裸鼠模型。
DOI：
10.1073/pnas.84.10.3390
复制
发表时间：
1987
影响因子：
11.1
通讯作者：
Seon,BK
中科院分区：
文献类型：
--
作者：
Hara,H;Seon,BK
在这项研究中，含有单克隆抗人T细胞白血病抗体的免疫毒素显示能够完全抑制体内人T细胞白血病细胞的肿瘤生长，而没有任何明显的不良毒性。这些免疫毒素是通过将蓖麻毒素A链（RA）与我们的单克隆抗体SN 1和SN 2偶联而制备的，这些抗体分别特异性针对人T细胞白血病细胞表面抗原TALLA和GP 37。我们已经表明，这些单克隆抗体对人T细胞白血病细胞具有高度特异性，并且不与各种正常细胞包括正常T和B细胞、胸腺细胞和骨髓细胞反应。在裸鼠中产生腹水和实体人T细胞白血病细胞肿瘤。腹水瘤通过将Ichikawa细胞（人T细胞白血病细胞系）腹膜内移植到裸鼠中产生，而实体瘤通过将Ichikawa细胞（人T细胞白血病细胞系）皮下移植到裸鼠中产生。MOLT-4细胞（一种人T细胞白血病细胞系）和经X射线照射的人纤维肉瘤细胞植入经X射线照射的裸鼠体内。为了研究特异性免疫毒素抑制腹水瘤体内生长的功效，我们将40只注射Ichikawa细胞的裸鼠分为四组。每组10只小鼠注射以下混合物之一：40微克纯化的对照小鼠IgG [IgG 1（κ）]（组1）、40微克对照RA缀合物（组2）、20微克纯化的SN 1抗体[IgG 1（κ）]和20微克纯化的SN 2抗体[IgG 1（κ）]（组3），或20 μ g SN 1-RA和20 μ g SN 2-RA（组4）。第1组和第2组小鼠形成大的腹水瘤，并在移植后5.8-7.0周死亡。第3组小鼠也形成了大的腹水瘤，并在移植后6.4-7.8周死亡。然而，在移植后随访的20周内，用SN 1-RA和SN 2-RA治疗的第4组小鼠中没有一只显示出任何肿瘤或不良毒性作用的迹象;这些小鼠与未注射Ichikawa细胞的健康对照裸鼠无法区分。用SN 1-RA加SN 2-RA治疗完全抑制了10只携带实体瘤的裸鼠中的4只的实体瘤生长，并部分抑制了剩余6只裸鼠的肿瘤生长。这些结果有力地表明，SN 1-RA和SN 2-RA可能是有用的临床治疗。
In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undesirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. We have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell line) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppressing the in vivo growth of the ascitic tumor, we divided 40 nude mice that were injected with Ichikawa cells into four groups. Each group of 10 mice was injected with one of the following mixtures: 40 micrograms of purified control mouse IgG [IgG1(kappa)] (group 1), 40 micrograms of control RA conjugate (group 2), 20 micrograms of purified SN1 antibody [IgG1(kappa)] and 20 micrograms of purified SN2 antibody [IgG1(kappa)] (group 3), or 20 micrograms of SN1-RA and 20 micrograms of SN2-RA (group 4). Mice in groups 1 and 2 formed large ascitic tumors, and died 5.8-7.0 weeks after the transplantation. Group 3 mice also formed large ascitic tumors and died 6.4-7.8 weeks after the transplantation. However, none of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation; these mice were indistinguishable from healthy control nude mice that were not injected with Ichikawa cells. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.