NKT cell-targeted vaccination plus anti-4-1BB antibody generates persistent CD8 T cell immunity against B cell lymphoma.
NKT cell-targeted vaccination plus anti-4-1BB antibody generates persistent CD8 T cell immunity against B cell lymphoma.
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DOI：
10.4161/2162402x.2014.990793
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发表时间：
2015-03
期刊：
影响因子：
7.2
通讯作者：
Mattarollo SR
中科院分区：
文献类型：
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作者：
Kobayashi T;Doff BL;Rearden RC;Leggatt GR;Mattarollo SR
利用自然杀伤 T (NKT) 细胞的免疫佐剂特性是产生抗癌免疫力的有效策略。本研究的目的是通过将装载 α-半乳糖神经酰胺 (α-GalCer) 的肿瘤细胞疫苗接种与针对免疫检查点分子 4-1BB (CD137) 的激动性抗体相结合，提高疫苗诱导的针对 B 细胞淋巴瘤免疫的效力和持久性。我们观察到，将疫苗接种与抗 4-1BB 抗体治疗相结合可产生有效的协同作用，从而显着提高携带 Eμ-myc 肿瘤的小鼠的存活率，包括完全根除超过 50% 的小鼠的淋巴瘤。无肿瘤生存需要 CD8+ T 细胞的干扰素 γ (IFNγ) 依赖性扩增，并与 KLRG1+ 效应 CD8+ T 细胞的 4-1BB 介导的分化相关。 “治愈”的小鼠在 80 天后也能抵抗淋巴瘤的再次攻击，这表明免疫记忆的成功生成。总体而言，我们的结果表明，使用 NKT 细胞配体针对 B 细胞淋巴瘤的治疗性抗癌疫苗接种可以通过随后通过 4-1BB 的共刺激来增强，从而产生可持续的免疫反应，从而可能增强传统治疗的效果。
Harnessing the immune adjuvant properties of natural killer T (NKT) cells is an effective strategy to generate anticancer immunity. The objective of this study was to increase the potency and durability of vaccine-induced immunity against B cell lymphoma by combining α-galactosylceramide (α-GalCer)-loaded tumor cell vaccination with an agonistic antibody targeting the immune checkpoint molecule 4–1BB (CD137). We observed potent synergy when combining vaccination and anti-4–1BB antibody treatment resulting in significantly enhanced survival of mice harboring Eμ-myc tumors, including complete eradication of lymphoma in over 50% of mice. Tumor-free survival required interferon γ (IFNγ)-dependent expansion of CD8+ T cells and was associated with 4–1BB-mediated differentiation of KLRG1+ effector CD8+ T cells. 'Cured' mice were also resistant to lymphoma re-challenge 80 days later indicating successful generation of immunological memory. Overall, our results demonstrate that therapeutic anticancer vaccination against B cell lymphoma using an NKT cell ligand can be boosted by subsequent co-stimulation through 4–1BB leading to a sustainable immune response that may enhance outcomes to conventional treatment.