Sykes M, Romick M L, Sachs D H
Transplantation Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5633-7. doi: 10.1073/pnas.87.15.5633.
We have recently demonstrated that interleukin 2 (IL-2), when administered in high doses for several days beginning on the day of allogeneic bone marrow transplantation (BMT), markedly diminishes graft-versus-host disease (GVHD) mortality in lethally irradiated mice. An optimal anti-GVHD effect was attained by coadministering T-cell-depleted (TCD) syngeneic marrow. We demonstrate here that the full graft-versus-leukemia effect of allogeneic T lymphocytes is obtained even when GVHD is markedly diminished by the coadministration of IL-2 and TCD syngeneic marrow. This methodology represents an approach to the treatment of leukemia in which the beneficial effects of allogeneic T cells can be exploited while their major deleterious effect, GVHD, is avoided. These results may thus have an impact on the clinical use of BMT for the treatment of hematologic malignancies.
我们最近证明,从同种异体骨髓移植(BMT)当天开始连续数天给予高剂量白细胞介素2(IL-2),可显著降低致死性照射小鼠的移植物抗宿主病(GVHD)死亡率。通过同时给予去除T细胞(TCD)的同基因骨髓可获得最佳的抗GVHD效果。我们在此证明,即使通过联合给予IL-2和TCD同基因骨髓显著降低了GVHD,仍可获得同种异体T淋巴细胞的完全移植物抗白血病效应。这种方法代表了一种治疗白血病的途径,即可以利用同种异体T细胞的有益作用,同时避免其主要有害作用GVHD。因此,这些结果可能会对BMT在血液系统恶性肿瘤治疗中的临床应用产生影响。