Immune response to Philadelphia chromosome-positive acute lymphoblastic leukemia induced by expression of CD80, interleukin 2, and granulocyte-macrophage colony-stimulating factor.
Immune response to Philadelphia chromosome-positive acute lymphoblastic leukemia induced by expression of CD80, interleukin 2, and granulocyte-macrophage colony-stimulating factor.
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CD80、白细胞介素 2 和粒细胞-巨噬细胞集落刺激因子的表达诱导对费城染色体阳性急性淋巴细胞白血病的免疫反应。
DOI：
10.1089/hum.1998.9.14-2049
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发表时间：
1998
影响因子：
4.2
通讯作者：
Kohn,DB
中科院分区：
文献类型：
--
作者：
Stripecke,R;Skelton,DC;Gruber,T;Afar,D;Pattengale,PK;Witte,ON;Kohn,DB
我们研究了产生针对费城染色体阳性急性淋巴细胞白血病的免疫应答的潜力。本研究选择的免疫刺激分子是细胞因子IL-2和GM-CSF以及共刺激配体CD 80（B7.1）。我们使用了基于BALB/c前B细胞系BM 185 wt的小鼠模型，其中白血病由p185 BCR-ABL致癌产物诱导，其复制费城染色体阳性ALL。用逆转录病毒载体转导BM 185 wt细胞，并将表达mIL-2、mGM-CSF或mCD 80的转导克隆用于攻击。BM 185细胞表达的免疫调节剂与免疫活性小鼠中白血病发展的延迟相关，但在免疫缺陷小鼠中不相关，表明针对修饰的白血病细胞的免疫应答。CD 80的表达导致50%的队列出现白血病排斥反应，这与抗白血病细胞毒性T淋巴细胞的CD 4+和CD 8 +T细胞依赖性发育有关。此外，在BM 185/CD 80攻击中存活的小鼠或用辐射的BM 185/CD 80细胞预免疫的小鼠产生了针对随后用亲本白血病攻击的免疫应答。这些研究提供的证据表明，免疫方法可以开发用于治疗ALL。
We examined the potential of generating an immune response against Philadelphia chromosome-positive acute lymphoblastic leukemia. The immunostimulatory molecules chosen for this study were the cytokines IL-2 and GM-CSF and the costimulatory ligand CD80 (B7.1). We used a murine model based on a BALB/c pre-B cell line, BM185wt, in which leukemia is induced by the p185 BCR-ABL oncogenic product, which reproduces Philadelphia chromosome-positive ALL. BM185wt cells were transduced with retroviral vectors and the transduced clones expressing mIL-2, mGM-CSF, or mCD80 were used for challenge. Expression of the immunomodulators by BM185 cells was correlated with delay in leukemia development in immunocompetent mice, but not in immunodeficient mice, indicating an immune response against the modified leukemia cells. Expression of CD80 caused leukemia rejection in 50% of the cohort, which was associated with the CD4+and CD8+T cell-dependent development of anti-leukemia cytotoxic T lymphocytes. Furthermore, mice surviving the BM185/CD80 challenge or preimmunized with irradiated BM185/CD80 cells developed an immune response against subsequent challenge with the parental leukemia. These studies provide evidence that immunotherapeutic approaches can be developed for the treatment of ALL.