Vaccine immunotherapy consisting of tumor antigens combined with an immune-enhancing adjuvant fosters cytotoxic T cell (CTL) proliferation. Clinically, polyI:C has been used as an adjuvant to enhance cancer vaccine protocols. However, according to its long history, polyI:C promotes inflammation that causes cytokine toxicity. Although checkpoint inhibitor immunotherapy has improved the prognoses of patients with progressive cancer, over 75% of patients continue to experience resistance to antibody (Ab) against anti-programmed cell death-protein 1 (PD-1) or its ligand, PD-L1 therapy. In most cases, patients suffer from adverse events resulting from inflammation during anti-PD-1/L1 Ab therapy, which is a serious obstacle to patients' quality of life. We have studied the functional properties of double-stranded (ds)RNA and polyI:C, and developed a nucleic acid adjuvant that barely induces a significant increase in the level of serum inflammatory cytokines in mouse models. This adjuvant, termed ARNAX, consists of DNA-capped dsRNA that specifies the endosomal target for Toll-like receptor 3 (TLR3) in dendritic cells (DCs). We expect that this adjuvant is safe for administration in elderly patients with cancer receiving immunotherapy. Here, we summarize the properties of ARNAX for immunotherapy in mice. We suggest that DC-priming is essential to induce anti-tumor immunity; neither exogenous inflammation nor the administration of tumor antigens is always a prerequisite for DC-mediated CTL proliferation. If our mouse data can be extrapolated to humans, ARNAX and the liberated endogenous tumor antigens may facilitate effect of current therapies on patients with therapy-resistant tumors.

中文翻译：

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用于治疗性免疫疗法的Toll样受体3（TLR3）激动剂ARNAX。

由肿瘤抗原和免疫增强佐剂组成的疫苗免疫疗法可促进细胞毒性T细胞（CTL）增殖。临床上，polyI：C已被用作增强癌症疫苗方案的佐剂。然而，根据其悠久的历史，polyI：C可促进引起细胞因子毒性的炎症。尽管检查点抑制剂免疫疗法改善了进行性癌症患者的预后，但仍有超过75％的患者继续抵抗针对抗程序性细胞死亡蛋白1（PD-1）或其配体PD-L1疗法的抗体（Ab） 。在大多数情况下，患者会因抗PD-1 / L1 Ab治疗期间的炎症而遭受不良事件的困扰，这是严重影响患者生活质量的障碍。我们研究了双链（ds）RNA和polyI：C的功能特性，并开发了一种核酸佐剂，几乎不引起小鼠模型中血清炎性细胞因子水平的显着提高。这种佐剂称为ARNAX，由DNA封端的dsRNA组成，该dsRNA指定树突状细胞（DC）中Toll样受体3（TLR3）的内体靶标。我们期望这种佐剂对于接受免疫疗法的老年癌症患者是安全的。在这里，我们总结了用于小鼠免疫治疗的ARNAX的特性。我们建议直流启动对于诱导抗肿瘤免疫至关重要。外源性炎症和施用肿瘤抗原都不是DC介导的CTL增殖的先决条件。如果我们的鼠标数据可以推断给人类，