Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers.
Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers.
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DOI：
10.3390/bioengineering10101205
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发表时间：
2023-10-16
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--
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尽管胰腺导管腺癌（PDAC）的治疗面临着巨大的挑战，但在通过开创性的纳米载体改善药物递送方面已经取得了相当大的进展。这些创新旨在克服发育异常基质所带来的障碍，并促进抗PDAC免疫反应。我们目前正在进行旨在通过诱导免疫原性细胞死亡（ICD）来增强化疗以刺激抗肿瘤免疫力的研究。这是使用脂质双层包衣的纳米载体实现的，其能够实现协同结果。值得注意的实例包括脂质体和被称为“二氧化硅体”的脂质包被的中孔二氧化硅纳米颗粒。这些纳米载体有助于远程化疗加载，以及免疫调节剂无缝整合到脂质双层中。在这次交流中，我们阐明了进一步改善化学免疫疗法的创新方法。第一个是通过远程加载伊立替康同时在脂质双层中掺入促分解脂氧素而设计的脂质体平台的开发。该载体干扰基质胶原沉积，以及促进伊立替康诱导的ICD反应。第二种方法是合成用于递送突变的KRAS肽与TLR 7/8激动剂的聚合物纳米颗粒。双重递送疫苗颗粒促进了抗原特异性细胞毒性T细胞的产生，所述细胞被募集到癌症部位的淋巴样结构，目的是加强通过化学免疫疗法实现的内源性疫苗接种应答。
Despite the formidable treatment challenges of pancreatic ductal adenocarcinoma (PDAC), considerable progress has been made in improving drug delivery via pioneering nanocarriers. These innovations are geared towards overcoming the obstacles presented by dysplastic stroma and fostering anti-PDAC immune reactions. We are currently conducting research aimed at enhancing chemotherapy to stimulate anti-tumor immunity by inducing immunogenic cell death (ICD). This is accomplished using lipid bilayer-coated nanocarriers, which enable the attainment of synergistic results. Noteworthy examples include liposomes and lipid-coated mesoporous silica nanoparticles known as “silicasomes”. These nanocarriers facilitate remote chemotherapy loading, as well as the seamless integration of immunomodulators into the lipid bilayer. In this communication, we elucidate innovative ways for further improving chemo-immunotherapy. The first is the development of a liposome platform engineered by the remote loading of irinotecan while incorporating a pro-resolving lipoxin in the lipid bilayer. This carrier interfered in stromal collagen deposition, as well as boosting the irinotecan-induced ICD response. The second approach was to synthesize polymer nanoparticles for the delivery of mutated KRAS peptides in conjunction with a TLR7/8 agonist. The dual delivery vaccine particle boosted the generation of antigen-specific cytotoxic T-cells that are recruited to lymphoid structures at the cancer site, with a view to strengthening the endogenous vaccination response achieved by chemo-immunotherapy.
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影响因子：
7.2
作者：
Dillard P;Casey N;Pollmann S;Vernhoff P;Gaudernack G;Kvalheim G;Wälchli S;Inderberg EM
通讯作者：
Inderberg EM
影响因子：
30.8
作者：
Chan-Seng-Yue, Michelle;Kim, Jaeseung C.;Notta, Faiyaz
通讯作者：
Notta, Faiyaz
影响因子：
24.5
作者：
Jacobetz MA;Chan DS;Neesse A;Bapiro TE;Cook N;Frese KK;Feig C;Nakagawa T;Caldwell ME;Zecchini HI;Lolkema MP;Jiang P;Kultti A;Thompson CB;Maneval DC;Jodrell DI;Frost GI;Shepard HM;Skepper JN;Tuveson DA
通讯作者：
Tuveson DA
影响因子：
13.6
作者：
Brennan, Eoin P.;Nolan, Karen A.;Godson, Catherine
通讯作者：
Godson, Catherine
影响因子：
6.4
作者：
Gjertsen, MK;Buanes, T;Gaudernack, G
通讯作者：
Gaudernack, G