Vourka-Karussis U, Karussis D, Ackerstein A, Slavin S
Department of Bone Marrow Transplantation, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
Exp Hematol. 1995 Mar;23(3):196-201.
A murine model for acute myeloid leukemia (mAML) was used to study graft-vs.-leukemia (GVL) effects on residual leukemic cells across both major (MHC) and minor histocompatibility antigens (mHA) barriers. In addition, the therapeutic effect of recombinant human interleukin-2 (rhIL-2)-administered postsyngeneic and allogeneic bone marrow transplantation (BMT) was examined. SJL/J mice inoculated with mAML cells were exposed later to total body irradiation (TBI) and transplanted with bone marrow cells (BMC) mixed with spleen cells derived from normal syngeneic (SJL/J), congenic (B10.S), or allogeneic (C57BL/6) donor mice. One-half of the mice in each group received low dose rhIL-2 for 3 days starting 1 day post-BMT. Spleen cells from treated recipients were transferred to secondary naive SJL/J mice for in vivo detection of residual tumor cells. At a tumor load of 10(5) cells per animal, none of the mice rescued with SJL/J or B10.S cells was cured since 100% of secondary recipients developed leukemia. Concomitant treatment of recipients of B10.S cells with rhIL-2 induced GVL effects since none of the secondary recipients developed leukemia after 2 years. All adoptive recipients of mice rescued with C57BL/6 cells remained free of leukemia after 2 years whether or not rhIL-2 was injected. The potency of the GVL effects observed across mHA and MHC were tumor-cell dose dependent since fewer animals inoculated with 10(6) mAML cells were cured. Only marginal GVL effects were noticed following syngeneic BMT and rhIL-2. Our results sustain the importance of the GVL effects in the treatment of myeloid leukemia and demonstrate that immunotherapy with rhIL-2 following BMT can enhance the therapeutic effect induced by the allograft.
利用急性髓系白血病小鼠模型（mAML）研究移植物抗白血病（GVL）对跨越主要（MHC）和次要组织相容性抗原（mHA）屏障的残留白血病细胞的作用。此外，还检测了重组人白细胞介素-2（rhIL-2）在同基因和异基因骨髓移植（BMT）后给药的治疗效果。接种mAML细胞的SJL/J小鼠随后接受全身照射（TBI），并移植与来自正常同基因（SJL/J）、同源（B10.S）或异基因（C57BL/6）供体小鼠的脾细胞混合的骨髓细胞（BMC）。每组一半的小鼠在BMT后1天开始接受低剂量rhIL-2治疗3天。将治疗后受体的脾细胞转移到次级未免疫的SJL/J小鼠中，用于体内检测残留肿瘤细胞。在每只动物肿瘤负荷为10(5)个细胞时，用SJL/J或B10.S细胞挽救的小鼠均未治愈，因为100%的次级受体发生了白血病。用rhIL-2同时治疗B10.S细胞受体可诱导GVL效应，因为2年后次级受体均未发生白血病。用C57BL/6细胞挽救的小鼠所有过继受体在2年后均未患白血病，无论是否注射rhIL-2。观察到的跨越mHA和MHC的GVL效应的效力是肿瘤细胞剂量依赖性的，因为接种10(6)个mAML细胞的动物中治愈的较少。同基因BMT和rhIL-2后仅观察到边缘性GVL效应。我们的结果证实了GVL效应在髓系白血病治疗中的重要性，并证明BMT后用rhIL-2进行免疫治疗可增强同种异体移植诱导的治疗效果。
