Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors.
Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors.
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DOI：
10.1007/s00262-011-1045-z
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Roy EJ
中科院分区：
文献类型：
--
作者：
Thomas DL;Doty R;Tosic V;Liu J;Kranz DM;McFadden G;Macneill AL;Roy EJ
肿瘤特异性 T 细胞的过继转移在治疗转移性黑色素瘤方面取得了一些成功。我们评估了一种新策略，通过对患有同基因 B16.SIY 黑色素瘤脑肿瘤的小鼠施用 T 细胞和溶瘤粘液瘤病毒来改善过继治疗。识别 SIY 肽的活化 CD8+ 2C T 细胞的过继转移使生存时间加倍，但 SIY 阴性肿瘤复发。粘液瘤病毒在体外杀死B16.SIY细胞，瘤内注射病毒导致肿瘤选择性短暂感染。病毒治疗将先天免疫细胞招募到肿瘤中，并诱导大脑中产生干扰素β，导致体内溶瘤作用有限。为了解决这个问题，我们评估了共同施用 2C T 细胞、粘液瘤病毒以及雷帕霉素或 IFNβ 中和抗体的安全性和有效性。接受三联疗法的小鼠存活时间明显更长，没有明显的副作用，但最终复发。重要的是，雷帕霉素治疗不会损害 T 细胞介导的肿瘤破坏，支持过继免疫疗法和雷帕霉素增强病毒疗法相结合的可行性。粘液瘤病毒可能是一种有用的载体，可将治疗基因瞬时递送至肿瘤以增强 T 细胞反应。
Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY melanoma brain tumors. Adoptive transfer of activated CD8+ 2C T cells that recognize SIY peptide doubled survival time, but SIY-negative tumors recurred. Myxoma virus killed B16.SIY cells in vitro, and intratumoral injection of virus led to selective and transient infection of the tumor. Virus treatment recruited innate immune cells to the tumor and induced IFNβ production in the brain, resulting in limited oncolytic effects in vivo. To counter this, we evaluated the safety and efficacy of co-administering 2C T cells, myxoma virus, and either rapamycin or neutralizing antibodies against IFNβ. Mice that received either triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Importantly, rapamycin treatment did not impair T cell-mediated tumor destruction, supporting the feasibility of combining adoptive immunotherapy and rapamycin-enhanced virotherapy. Myxoma virus may be a useful vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses.
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DOI：
10.1038/nrmicro1099
发表时间：
2005-03
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Dunn, GP;Sheehan, KCF;Schreiber, RD
通讯作者：
Schreiber, RD
影响因子：
11.5
作者：
Kline, Justin;Brown, Ian E.;Gajewski, Thomas F.
通讯作者：
Gajewski, Thomas F.
影响因子：
11.2
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF
影响因子：
6.4
作者：
Alonso, M. M.;Gomez-Manzano, C.;Fueyo, J.
通讯作者：
Fueyo, J.