Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors
Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors
复制标题
DOI：
10.1182/blood.v93.2.643.402k24_643_654
复制
发表时间：
1999-01-15
期刊：
影响因子：
20.3
通讯作者：
Rosenblatt, JD
中科院分区：
文献类型：
--
作者：
Kutubuddin, M;Federoff, HJ;Rosenblatt, JD
研究了表达RANTES（HSVrantes）和T细胞共刺激配体B7.1（HSVB7.1）的单纯疱疹病毒扩增子载体在小鼠淋巴瘤模型中引发肿瘤特异性T细胞应答的能力。通过流式细胞术和酶联免疫吸附试验分别分析，HSVB7.1和HSVrantes转导的EL 4细胞表达高水平的B7.1和RANTES。在同基因小鼠中接种离体HSVB7.1转导的细胞导致对侧接种的转导细胞和非转导细胞的消退。将HSVB7.1和/或HSVrantes单独或组合直接瘤内注射到建立的EL 4肿瘤中导致注射的肿瘤以及未转导的对侧植入的肿瘤中的完全肿瘤消退，而用表达β-半乳糖苷酶的HSVlac注射的肿瘤的对照肿瘤没有消退。通过联合注射HSVB7.1和HSVrantes实现最大保护：显示肿瘤消退的小鼠对用亲本EL 4细胞再攻击具有抗性，并且在显示消退的小鼠中观察到肿瘤细胞特异性细胞溶解T细胞活性。HSV扩增子介导的免疫效应分子的递送可能代表了在预先存在的肿瘤的情况下用于免疫治疗的有用策略。(C)1999年，美国血液学会。
Herpes simplex virus amplicon vectors expressing RANTES (HSVrantes) and the T-cell costimulatory ligand B7.1 (HSVB7.1) were studied for their ability to elicit a tumor-specific T-cell response in a murine lymphoma model. HSVB7.1- and HSVrantes-transduced EL4 cells expressed high levels of B7.1 and RANTES as analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. Inoculation of ex vivo HSVB7.1 transduced cells in syngeneic mice resulted in regression of both transduced cells and nontransduced cells inoculated contralaterally. Direct intratumoral injection of HSVB7.1 and/or HSVrantes alone or in combination into established EL4 tumors led to complete tumor regression in injected tumors as well as in nontransduced contralaterally implanted tumor, whereas control tumors OF tumors injected with HSVlac expressing beta-galactosidase did not regress. Maximal protection was achieved with combined injection of HSVB7.1, and HSVrantes: mice showing tumor regression were resistant to rechallenge with parental EL4 cells, and tumor cell-specific cytolytic T-cell activity was observed in mice demonstrating regression. HSV amplicon-mediated delivery of immune effector molecules may represent a useful strategy for immunotherapy in the setting of pre-existing tumor. (C) 1999 by The American Society of Hematology.