A CpG-loaded tumor cell vaccine induces antitumor CD4+ T cells that are effective in adoptive therapy for large and established tumors
A CpG-loaded tumor cell vaccine induces antitumor CD4+ T cells that are effective in adoptive therapy for large and established tumors
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DOI：
10.1182/blood-2010-06-288456
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发表时间：
2011-01-06
期刊：
影响因子：
20.3
通讯作者：
Levy, Ronald
中科院分区：
文献类型：
--
作者：
Goldstein, Matthew J.;Varghese, Bindu;Levy, Ronald
我们设计了一种全肿瘤细胞疫苗，通过“加载”淋巴瘤肿瘤细胞与CG富集的寡脱氧核苷酸（CpG），Toll样受体9（TLR 9）的配体。吞噬负载CpG的肿瘤细胞，将肿瘤抗原和免疫刺激性CpG分子递送至抗原呈递细胞（APC）。然后，这些APC表达水平增加的共刺激分子和诱导的T细胞免疫。TLR 9在APC中是必需的，而在负载CpG的肿瘤细胞中不是。我们证明，这种疫苗诱导的T细胞是有效的过继细胞治疗淋巴瘤。来自接种疫苗的小鼠的T细胞转移到经辐照的同基因受体中，可以保护其免受随后的淋巴瘤攻击，并且显著地导致大的和已建立的肿瘤的消退。这种治疗作用可通过CD 4（+）T细胞而不是CD 8（+）T细胞传递。负载CpG的全细胞疫苗接种是实用的，并且具有很强的转化为临床环境的潜力。它目前正在进行临床试验，过继免疫治疗套细胞淋巴瘤。（血。2011;117（1）：118-127）
We designed a whole tumor cell vaccine by "loading" lymphoma tumor cells with CG-enriched oligodeoxynucleotide (CpG), a ligand for the Toll-like receptor 9 (TLR9). CpG-loaded tumor cells were phagocytosed, delivering both tumor antigen(s) and the immunostimulatory CpG molecule to antigen-presenting cells (APCs). These APCs then expressed increased levels of costimulatory molecules and induced T-cell immunity. TLR9 was required in the APCs but not in the CpG-loaded tumor cell. We demonstrate that T cells induced by this vaccine are effective in adoptive cellular therapy for lymphoma. T cells from vaccinated mice transferred into irradiated, syngeneic recipients protected against subsequent lymphoma challenge and, remarkably, led to regression of large and established tumors. This therapeutic effect could be transferred by CD4(+) but not by CD8(+) T cells. A CpG-loaded whole-cell vaccination is practical and has strong potential for translation to the clinical setting. It is currently being tested in a clinical trial of adoptive immunotherapy for mantle-cell lymphoma. (Blood. 2011;117(1):118-127)