In Situ Tumor Vaccination with Nanoparticle Co-Delivering CpG and STAT3 siRNA to Effectively Induce Whole-Body Antitumor Immune Response.
In Situ Tumor Vaccination with Nanoparticle Co-Delivering CpG and STAT3 siRNA to Effectively Induce Whole-Body Antitumor Immune Response.
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DOI：
10.1002/adma.202100628
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Yantasee W
中科院分区：
文献类型：
--
作者：
Ngamcherdtrakul W;Reda M;Nelson MA;Wang R;Zaidan HY;Bejan DS;Hoang NH;Lane RS;Luoh SW;Leachman SA;Mills GB;Gray JW;Lund AW;Yantasee W
免疫检查点抑制剂（ICI）在一部分个体中的免疫治疗取得的成功非常令人兴奋。然而，在许多癌症中，对当前ICI的反应是适度的，并且仅在一小部分患者中观察到。在这里，一个广泛适用的方法，增加了ICI的好处。肿瘤内施用增强免疫应答和抑制肿瘤的抑制性环境-共递送CpG和STAT 3 siRNA的AIRISE-02纳米颗粒不仅导致注射的肿瘤消退，而且导致多个肿瘤模型系统中远处部位的肿瘤消退。特别地，三个剂量的AIRISE-02与全身性ICI的组合在8只小鼠中的5只中完全治愈了治疗的和未治疗的侵袭性黑素瘤肿瘤，而单独的ICI不能治愈任何小鼠。还报道了长期记忆免疫效应。AIRISE-02在乳腺和结肠肿瘤模型中也有效。最后，AIRISE-02在小鼠和非人灵长类动物中耐受性良好。这种方法将多种治疗剂结合到单个纳米结构中，以在多种癌症类型中产生全身免疫反应。作为一种局部治疗药物，AIRISE-02规避了全身性纳米颗粒递送的监管挑战，促进了快速转化为临床。AIRISE-02正在进行IND研究，临床试验将很快进行。AIRISE-02是一种纳米免疫治疗候选药物，可将CpG和STAT 3 siRNA共同递送至局部肿瘤，并在体内各处产生针对癌症的抗肿瘤免疫应答。AIRISE-02抑制小鼠的局部和未治疗的远处肿瘤。AIRISE-02和标准免疫检查点抑制剂的组合治愈了60%的黑色素瘤小鼠，而单独使用抑制剂则无法治愈。
The success of immunotherapy with immune checkpoint inhibitors (ICIs) in a subset of individuals has been very exciting. However, in many cancers, the responses to current ICIs are modest and seen only in small subsets of patients. Herein, a widely applicable approach that increases the benefit of ICIs is reported. Intratumoral administration of Augmenting Immune Response and Inhibiting Suppressive Environment of tumors – AIRISE-02 nanotherapeutic that co-delivers CpG and STAT3 siRNA results in not only regression of the injected tumor, but also tumors at distant sites in multiple tumor model systems. In particular, three doses of AIRISE-02 in combination with systemic ICIs completely cure both treated and untreated aggressive melanoma tumors in 5 out of 8 mice, while ICIs alone do not cure any mice. Long-term memory immune effect is also reported. AIRISE-02 is effective in breast and colon tumor models, as well. Lastly, AIRISE-02 is well tolerated in mice and non-human primates. This approach combines multiple therapeutic agents into a single nanoconstruct to create whole-body immune responses across multiple cancer types. Being a local therapeutic, AIRISE-02 circumvents regulatory challenges of systemic nanoparticle delivery, facilitating rapid translation to the clinic. AIRISE-02 is under IND-enabling studies, and clinical trials will soon follow. AIRISE-02 is a nano-immunotherapy candidate that co-delivers CpG and STAT3 siRNA to a local tumor, and generates anti-tumor immune response against cancer everywhere in the body. AIRISE-02 inhibits both local and untreated distant tumors in mice. Combination of AIRISE-02 and standard immune checkpoint inhibitors cures 60% of mice with melanoma tumors, while the inhibitors alone cure none.
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