Combination of CD80 and granulocyte-macrophage colony-stimulating factor coexpression by a leukemia cell vaccine: preclinical studies in a murine model recapitulating Philadelphia chromosome-positive acute lymphoblastic leukemia.
Combination of CD80 and granulocyte-macrophage colony-stimulating factor coexpression by a leukemia cell vaccine: preclinical studies in a murine model recapitulating Philadelphia chromosome-positive acute lymphoblastic leukemia.
复制标题
白血病细胞疫苗联合表达 CD80 和粒细胞-巨噬细胞集落刺激因子：在模拟费城染色体阳性急性淋巴细胞白血病的小鼠模型中进行临床前研究。
DOI：
10.1089/10430349950017103
复制
发表时间：
1999
影响因子：
4.2
通讯作者：
D. B. Kohn
中科院分区：
文献类型：
--
作者：
R. Stripecke;D. Skelton;P. Pattengale;H. Shimada;D. B. Kohn
费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）是由bcr-abl易位癌基因引起的高度侵袭性恶性肿瘤。为了探索Ph+ ALL的替代治疗方法，我们在BALB/c衍生的BM 185白血病模型中测试了基因修饰的细胞疫苗。我们比较了单独表达CD 80或与IL-2或GM-CSF组合表达CD 80的BM 185细胞疫苗的功效。用经修饰以表达CD 80和GM-CSF的活的BM 185白血病细胞（BM 185/CD 80 +GM-CSF）注射的小鼠显示出最高的白血病排斥率。由经辐照的BM 185/CD 80 +GM-CSF细胞组成的细胞疫苗皮下施用刺激针对亲本BM 185的有效细胞毒性T淋巴细胞（CTL）应答。接种部位的组织学检查显示免疫细胞浓度较高。在用亲本细胞静脉内攻击之前施用BM 185/CD 80 +GM-CSF细胞疫苗引起白血病发展的强烈抑制。用BM 185细胞皮下攻击后的疫苗接种引起白血病的有效消除，促进40-60%的长期存活率。BM 185/CD 80 + GM-CSF细胞疫苗的免疫效力与表达转基因的细胞的百分比直接相关。总之，这项临床前研究表明，共表达CD 80和GM-CSF的白血病细胞疫苗可用于Ph+ ALL患者的免疫治疗。
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a highly aggressive malignancy caused by the bcr-abl translocation oncogene. To explore alternative treatments for Ph+ ALL we tested gene-modified cell vaccines in the BALB/c-derived BM185 leukemia model. We compared the efficacy of BM185 cell vaccine expressing CD80 alone or in combination with IL-2 or GM-CSF. Mice injected with viable BM185 leukemia cells modified to express CD80 and GM-CSF (BM185/CD80+GM-CSF) showed the highest leukemia rejection rates. Cell vaccines consisting of irradiated BM185/CD80+GM-CSF cells administered subcutaneously stimulated a potent cytotoxic T lymphocyte (CTL) response against parental BM185. Histological examination of the vaccination site showed a large concentration of immune cells. Administration of the BM185/CD80+GM-CSF cell vaccine before intravenous challenge with parental cells caused strong inhibition of leukemia development. Vaccination after subcutaneous challenge with BM185 cells caused efficient elimination of leukemia promoting 40-60% long-term survival rates. The immunization efficacy of the BM185/CD80+ GM-CSF cell vaccine was directly correlated with the percentage of cells expressing the transgenes. In all, this preclinical study shows that leukemia cell vaccines coexpressing CD80 and GM-CSF can potentially be explored for immunotherapy in Ph+ ALL patients.
登录
查看更多内容
影响因子：
20.3
作者：
C. Westbrook;A. Hooberman;C. Spino;R. Dodge;R. Larson;F. Davey;D. Wurster‐Hill;R. Sobol;C. Schiffer;C. Bloomfield
通讯作者：
C. Westbrook;A. Hooberman;C. Spino;R. Dodge;R. Larson;F. Davey;D. Wurster‐Hill;R. Sobol;C. Schiffer;C. Bloomfield
影响因子：
15.9
作者：
LOPEZ, AF;WILLIAMSON, DJ;VADAS, MA
通讯作者：
VADAS, MA
影响因子：
20.3
作者：
Bocchia, M;Korontsvit, T;Scheinberg, DA
通讯作者：
Scheinberg, DA
Pre-B 急性淋巴细胞白血病细胞可能诱导 T 细胞对同种异体抗原无反应。
影响因子：
20.3
作者：
Cardoso,AA;Schultze,JL;Boussiotis,VA;Freeman,GJ;Seamon,MJ;Laszlo,S;Billet,A;Sallan,SE;Gribben,JG;Nadler,LM
通讯作者：
Nadler,LM
影响因子：
4.2
作者：
Kong, HL;Hecht, D;Crystal, RG
通讯作者：
Crystal, RG