Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Blood. 2011 Jan 6;117(1):118-27. doi: 10.1182/blood-2010-06-288456. Epub 2010 Sep 27.
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.
我们设计了一种全肿瘤细胞疫苗，通过“装载”富含 CG 的寡脱氧核苷酸（CpG）的淋巴瘤肿瘤细胞，CpG 是 Toll 样受体 9（TLR9）的配体。CpG 负载的肿瘤细胞被吞噬，向抗原呈递细胞（APC）传递肿瘤抗原和免疫刺激性 CpG 分子。这些 APC 然后表达更高水平的共刺激分子，并诱导 T 细胞免疫。TLR9 在 APC 中是必需的，但在 CpG 负载的肿瘤细胞中不是必需的。我们证明，这种疫苗诱导的 T 细胞在淋巴瘤的过继细胞治疗中是有效的。从接种疫苗的小鼠中转移到辐照的同基因受体内的 T 细胞可预防随后的淋巴瘤攻击，并且令人惊讶的是，可导致大型和已建立的肿瘤消退。这种治疗效果可以通过 CD4(+)但不是 CD8(+)T 细胞转移。CpG 负载的全细胞疫苗接种是实用的，具有很强的转化为临床环境的潜力。目前正在进行一项临床试验，评估其在套细胞淋巴瘤的过继免疫治疗中的作用。
