There is no doubt that immunotherapy lies in the spotlight of current cancer research and clinical trials. However, there are still limitations in the treatment response in certain types of tumors largely due to the presence of the complex network of immunomodulatory and immunosuppressive pathways. These limitations are not likely to be overcome by current immunotherapeutic options, which often target isolated steps in immune pathways preferentially involved in adaptive immunity. Recently, we have developed an innovative anti-cancer immunotherapeutic strategy that initially elicits a strong innate immune response with subsequent activation of adaptive immunity in mouse models. Robust primary innate immune response against tumor cells is induced by toll-like receptor ligands and anti-CD40 agonistic antibodies combined with the phagocytosis-stimulating ligand mannan, anchored to a tumor cell membrane by biocompatible anchor for membrane. This immunotherapeutic approach results in a dramatic therapeutic response in large established murine subcutaneous tumors including melanoma, sarcoma, pancreatic adenocarcinoma, and pheochromocytoma. Additionally, eradication of metastases and/or long-lasting resistance to subsequent re-challenge with tumor cells was also accomplished. Current and future advantages of this immunotherapeutic approach and its possible combinations with other available therapies are discussed in this review.

中文翻译：

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Coley的免疫疗法得以复兴：先天免疫是引发癌细胞针对适应性免疫发起攻击的一个环节。

毫无疑问，免疫疗法是当前癌症研究和临床试验的重点。然而，在某些类型的肿瘤中，由于多种免疫调节和免疫抑制途径的复杂网络的存在，治疗反应仍然存在局限性。当前的免疫治疗选择不可能克服这些限制，这些选择通常针对优先参与适应性免疫的免疫途径中孤立的步骤。最近，我们开发了一种创新的抗癌免疫治疗策略，该策略最初会引起强烈的先天免疫反应，随后激活小鼠模型中的适应性免疫。Toll样受体配体和抗CD40激动抗体与吞噬作用刺激配体甘露聚糖结合，通过生物相容性膜锚定锚定在肿瘤细胞膜上，从而诱导出针对肿瘤细胞的强大的先天免疫应答。这种免疫治疗方法在大型已确定的鼠皮下肿瘤（包括黑素瘤，肉瘤，胰腺腺癌和嗜铬细胞瘤）中产生了戏剧性的治疗反应。另外，还实现了根除转移和/或对随后用肿瘤细胞再次攻击的持久抗性。在这篇综述中讨论了这种免疫治疗方法的当前和未来优势以及它与其他可用疗法的可能组合。这种免疫治疗方法在大型已确定的鼠皮下肿瘤（包括黑素瘤，肉瘤，胰腺腺癌和嗜铬细胞瘤）中产生了戏剧性的治疗反应。另外，还实现了根除转移和/或对随后用肿瘤细胞再次攻击的持久抗性。在这篇综述中讨论了这种免疫治疗方法的当前和未来优势以及它与其他可用疗法的可能组合。这种免疫治疗方法在大型已确定的鼠皮下肿瘤（包括黑素瘤，肉瘤，胰腺腺癌和嗜铬细胞瘤）中产生了戏剧性的治疗反应。另外，还实现了根除转移和/或对随后用肿瘤细胞再次攻击的持久抗性。在这篇综述中讨论了这种免疫治疗方法的当前和未来优势以及它与其他可用疗法的可能组合。