Fujii S, Shimizu K, Fujimoto K, Kiyokawa T, Shimomura T, Kinoshita M, Kawano F
The Center for Bone Marrow Transplantation and Immunotherapy, Institute for Clinical Research, Kumamoto National Hospital, Ninomaru.
Jpn J Cancer Res. 1999 Oct;90(10):1117-29. doi: 10.1111/j.1349-7006.1999.tb00686.x.
Dendritic cells (DCs) are believed to be the most potent antigen-presenting cells and may be important in the induction of anti-leukemia specific T cell responses. In this preliminary clinical study, a patient with chronic phase chronic myelogenous leukemia (CML) was vaccinated with autologous leukemic DCs following autologous peripheral blood stem cell transplantation (PBSCT). In an in vitro study, leukemic DCs were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha, and interleukin-4 from granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC fraction of this patient, and were found to be Ph1+, and to possess the morphologic and phenotypic characteristics of mature DCs. These cells could also elicit antigen specific immune responses, including a vigorous cytotoxicity specific to CML cells. In the clinical experiment, we obtained evidence that infused leukemic DCs could induce T cell clones expressing the same T cell receptor usage as a cytotoxic T cell line, suggesting that the immune repertoire includes tumor-reactive T cells. These cytotoxic T lymphocytes are activated in vivo. The vaccination of leukemic DC caused a decrease in the number of Ph1+ cells in the peripheral blood and bone marrow. These results indicate that the activity is an immunologically mediated phenomenon and vaccination therapy with leukemic DC following autologous PBSCT may be effective in treating CML.
树突状细胞(DCs)被认为是最有效的抗原呈递细胞,在诱导抗白血病特异性T细胞反应中可能起重要作用。在这项初步临床研究中,一名慢性期慢性粒细胞白血病(CML)患者在自体外周血干细胞移植(PBSCT)后接种了自体白血病DCs。在一项体外研究中,使用粒细胞-巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子-α和白细胞介素-4,从该患者的粒细胞集落刺激因子(G-CSF)动员的PBSC组分中生成白血病DCs,发现其为Ph1阳性,并具有成熟DCs的形态和表型特征。这些细胞还能引发抗原特异性免疫反应,包括对CML细胞的强烈细胞毒性。在临床实验中,我们获得的证据表明,注入的白血病DCs可诱导表达与细胞毒性T细胞系相同T细胞受体用法的T细胞克隆,这表明免疫库中包括肿瘤反应性T细胞。这些细胞毒性T淋巴细胞在体内被激活。白血病DCs疫苗接种导致外周血和骨髓中Ph1阳性细胞数量减少。这些结果表明,该活性是一种免疫介导的现象,自体PBSCT后用白血病DCs进行疫苗接种治疗可能对治疗CML有效。