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首页> 外文期刊>Journal of Translational Medicine >Specific targeting of whole lymphoma cells to dendritic cells ex vivo provides a potent antitumor vaccine
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Specific targeting of whole lymphoma cells to dendritic cells ex vivo provides a potent antitumor vaccine

机译：将整个淋巴瘤细胞特异性靶向离体树突状细胞可提供有效的抗肿瘤疫苗

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Background Dendritic cells (DC) pulsed with tumor-derived antigenic material have widely been used in antitumor vaccination protocols. However, the optimal strategy of DC loading has not yet been established. Our aim was to define requirements of optimal DC vaccines in terms of in vivo protection in a murine B-cell lymphoma model. Methods We compare various loading reagents including whole parental and modified tumor cells and a single tumor-specific antigen, namely the lymphoma idiotype (Id). Bone marrow-derived DC were pulsed in vitro and used for therapy of established A20 lymphomas. Results We show that a vaccine with superior antitumor efficacy can be generated when DC are loaded with whole modified tumor cells which provide both (i) antigenic polyvalency and (ii) receptor-mediated antigen internalization. Uptake of cellular material was greatly enhanced when the tumor cells used for DC pulsing were engineered to express an anti-Fc receptor immunoglobulin specificity. Upon transfer of these DC, established tumor burdens were eradicated in 50% of mice. By contrast, pulsing DC with unmodified lymphoma cells or with the lymphoma Id, even when it was endowed with the anti-Fc receptor binding arm, was far less effective. A specific humoral anti-Id response could be detected, particularly following delivery of Id protein-pulsed DC, but it was not predictive of tumor protection. Instead a T-cell response was pivotal for successful tumor protection. Interaction of the transferred DC with CD8+ T lymphocytes seemed to play a role for induction of the immune response but was dispensable when DC had received an additional maturation stimulus. Conclusion Our analyses show that the advantages of specific antigen redirection and antigenic polyvalency can be combined to generate DC-based vaccines with superior antitumor efficacy. This mouse model may provide information for the standardization of DC-based vaccination protocols.
机译：背景技术用肿瘤来源的抗原物质脉冲的树突状细胞（DC）已广泛用于抗肿瘤疫苗接种方案。但是，尚未建立DC负载的最佳策略。我们的目的是根据鼠B细胞淋巴瘤模型的体内保护定义最佳DC疫苗的要求。方法我们比较了各种加载试剂，包括整个亲代和修饰的肿瘤细胞以及单个肿瘤特异性抗原，即淋巴瘤独特型（Id）。在体外对源自骨髓的DC进行脉冲治疗，并将其用于治疗已建立的A20淋巴瘤。结果我们显示，当DC装有完整的修饰肿瘤细胞时，可以产生具有优异抗肿瘤功效的疫苗，该肿瘤细胞既提供（i）抗原多价性，又提供（ii）受体介导的抗原内化作用。当将用于DC脉冲的肿瘤细胞改造成表达抗Fc受体免疫球蛋白特异性时，细胞物质的摄取大大提高。这些DC转移后，已建立的肿瘤负担在50％的小鼠中得以消除。相比之下，即使未修饰的淋巴瘤细胞或淋巴瘤Id带有抗Fc受体结合臂，对DC施加脉冲的效果也要差得多。可以检测到特定的体液抗-Id反应，尤其是在递送Id蛋白脉冲的DC后，但不能预测肿瘤的保护作用。相反，T细胞反应对于成功保护肿瘤至关重要。转移的DC与CD8 + T淋巴细胞的相互作用似乎在诱导免疫应答中起一定作用，但是当DC受到额外的成熟刺激时，这种相互作用是可有可无的。结论我们的分析表明，可以将特异性抗原重定向和抗原多价的优势相结合，以产生具有优异抗肿瘤功效的DC型疫苗。该鼠标模型可以为基于DC的疫苗接种协议的标准化提供信息。

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