The use of dendritic cells (DCs) loaded with apoptotic tumor cells is an attractive approach to tumor vaccination in the absence of well-characterized tumor antigens. Apoptotic tumor cells are a convenient source of polyvalent tumor antigen, but may induce only weak immunization. We tested the role of replication-incompetent recombinant herpes simplex virus (HSV) d106 lacking all immediate early genes except ICP0 in the generation of apoptotic cells for tumor vaccination, using ID8-VEGF, a syngeneic mouse model of ovarian carcinoma expressing high levels of VEGF, and TC-1, a human papillomavirus (HPV) 16 E6- and E7-transformed adenocarcinoma. HSVd106 killed tumor cells by apoptosis. Tumor cells infected by HSVd106 were engulfed more avidly by immature DCs, and induced DC maturation more efficiently than tumor cells killed by ultraviolet B (UVB) radiation. HSVd106 infection induced stronger upregulation of heat shock protein (Hsp) 70 and glucose-related protein (GRP) 94 than UVB in cells undergoing apoptosis. Immunization of mice with DCs loaded with HSVd106-killed cells elicited stronger antitumor T-cell response, including tumor-reactive interferon-gamma-secreting and cytotoxic T cells, and resulted in significantly stronger delay in tumor growth than immunization with DCs loaded with UVB-killed tumor cells. Moreover, in the TC-1 model, a protective effect of vaccination (40% tumor free animals) was observed only after immunization with DCs loaded with HSVd106-killed cells. Thus, the use of replication-incompetent HSV strains lacking immediate early genes except ICP0 offers possible advantages in the preparation of whole tumor cell antigen for DC-based tumor vaccination.

中文翻译：

---

用无复制能力的HSV制备凋亡性肿瘤细胞可增强树突状细胞疫苗的功效。

在缺乏特征明确的肿瘤抗原的情况下，使用载有凋亡性肿瘤细胞的树突状细胞（DC）是一种有吸引力的肿瘤疫苗接种方法。凋亡的肿瘤细胞是多价肿瘤抗原的方便来源，但可能仅诱导弱免疫。我们使用ID8-VEGF（一种表达高水平VEGF的卵巢癌同系小鼠模型），测试了除了ICP0以外，所有其他早期无早期复制基因的无复制能力的单纯疱疹病毒（HSV）d106在肿瘤细胞凋亡中的作用和TC-1，即人乳头瘤病毒（HPV）16 E6-和E7转化的腺癌。HSVd106通过凋亡杀死肿瘤细胞。HSVd106感染的肿瘤细胞更容易被未成熟的DC吞噬，并比被紫外线B（UVB）辐射杀死的肿瘤细胞更有效地诱导DC成熟。在经历凋亡的细胞中，HSVd106感染比UVB诱导了更强的热休克蛋白（Hsp）70和葡萄糖相关蛋白（GRP）94上调。用装有HSVd106杀死的细胞的DC免疫小鼠会引起更强的抗肿瘤T细胞反应，包括肿瘤反应性干扰素-γ分泌和细胞毒性T细胞，并且与用UVB-DC的DC免疫相比，肿瘤生长的延迟明显更长。杀死肿瘤细胞。此外，在TC-1模型中，仅在用载有HSVd106杀伤细胞的DC免疫后才观察到疫苗接种（无肿瘤动物40％）的保护作用。从而，