Retroviral vectors for production of interleukin-12 in the bone marrow to induce a graft-versus-leukemia effect
Retroviral vectors for production of interleukin-12 in the bone marrow to induce a graft-versus-leukemia effect
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DOI：
10.1111/j.1749-6632.1996.tb52687.x
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Hawley, TS
中科院分区：
文献类型：
--
作者：
Hawley, RG;Lieu, FHL;Hawley, TS
自体干细胞移植 (ASCT) 越来越多地与大剂量放化疗结合使用，用于治疗血液恶性肿瘤。随着积极选择动员到外周血中的正常造血干细胞的改进方法的发展，自体移植物中回输污染性白血病细胞的风险应该会降低。*然而，与 ASCT 相关的复发的主要原因是 据认为，这是由于无法破坏残留的白血病细胞，因为缺乏类似于接受同种异体移植的患者中供体 T 细胞介导的移植物抗白血病效应^。^ 最近认识到移植物抗白血病效应可以与同种异体移植物中的移植物抗宿主病分开，这提高了在 ASCT 后操纵免疫系统以根除微小疾病的可能性。 保护正常造血细胞^.^,^ 白细胞介素 (IL)-12 在小鼠肿瘤模型中诱导有效抗肿瘤转移活性的能力 6-' 加上它作为造血干细胞/祖细胞的协同生长因子的事实，8 与它抑制急性移植物抗宿主病的意外发现一起考虑，表明该细胞因子的潜在应用 ASCT 后刺激移植物抗白血病反应的辅助疗法。 lo 作为造血过程中在骨髓中实现免疫调节细胞因子高局部产生的一种手段-a 这项工作得到了加拿大国家癌症研究所和加拿大医学研究委员会的资助。
Autologous stem cell transplantation (ASCT) is being increasingly used in conjunction with high-dose chemoradiotherapy for treatment of hematologic malignancies.’With the development of improved methods to positively select normal hematopoietic stem cells mobilized into the peripheral blood should come a reduced risk of reinfusing contaminating leukemic cells in the autograft.* However, the major cause of relapse associated with ASCT is believed to be due to the inability to destroy residual leukemic cells because of the lack of a graft-versusleukemia effect analogous to that mediated by donor T cells in patients receiving allograft^.^ The recent appreciation that the graft-versus-leukemia effect can be separated from graft-versus-host disease in the allograft setting has raised the possibility of manipulating the immune system after ASCT to eradicate minimal disease while sparing normal hematopoietic cell^.^,^ The ability of interleukin (IL)-12 to induce potent antitumoriantimetastatic activity in murine tumor models6-’plus the fact that it acts as a synergistic growth factor for hematopoietic stem/progenitor cells, 8 considered together with the unexpected finding that it inhibits acute graft-versus-host disease in suggests potential application of this cytokine as an adjuvant therapy to stimulate a graftversus-leukemia reaction following ASCT. lo As a means of achieving high local production of immunoregulatory cytokines in the bone marrow during hematopoi-a This work was supported by grants from the National Cancer Institute of Canada and the Medical Research Council of Canada.