Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines.
Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines.
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DOI：
10.1021/acsnano.0c02765
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发表时间：
2020-08-25
期刊：
影响因子：
17.1
通讯作者：
Wilson JT
中科院分区：
文献类型：
--
作者：
Shae D;Baljon JJ;Wehbe M;Christov PP;Becker KW;Kumar A;Suryadevara N;Carson CS;Palmer CR;Knight FC;Joyce S;Wilson JT
针对患者特异性新抗原的癌症疫苗已成为改善免疫检查点阻断反应的有前途的策略。然而，新抗原肽的免疫原性较差，并且无法刺激 CD8+ T 细胞反应，因此需要增强其免疫原性的新疫苗技术。干扰素基因刺激剂 (STING) 途径是一种内源性机制，先天免疫系统通过该机制产生免疫环境，以启动和动员新抗原特异性 T 细胞。由于在肿瘤免疫监视中的这一关键作用，开发了一种合成癌症纳米疫苗平台 (nanoSTING-vax)，它可以模仿免疫原性癌细胞，有效促进肽抗原和 STING 激动剂 cGAMP 的共同传递。将 cGAMP 和肽共同装载到 pH 响应性内体溶解聚合物囊中，促进 cGAMP 和肽抗原协调递送至胞质溶胶，从而引发炎症细胞因子的产生、共刺激标记物表达和抗原交叉呈递。因此，nanoSTING-vax 显着增强了 CD8+ T 细胞对一系列肽抗原的反应。 nanoSTING-vax 的治疗性免疫结合免疫检查点阻断，抑制了多种小鼠肿瘤模型中的肿瘤生长，甚至导致肿瘤完全排斥并产生持久的抗肿瘤免疫记忆。总的来说，这项工作将 nanoSTING-vax 建立为一个多功能平台，用于增强对新抗原靶向癌症疫苗的免疫反应。
Cancer vaccines targeting patient-specific neoantigens have emerged as a promising strategy for improving responses to immune checkpoint blockade. However, neoantigenic peptides are poorly immunogenic and inept at stimulating CD8+ T cell responses, motivating a need for new vaccine technologies that enhance their immunogenicity. The stimulator of interferon genes (STING) pathway is an endogenous mechanism by which the innate immune system generates an immunological context for priming and mobilizing neoantigen-specific T cells. Owing to this critical role in tumor immune surveillance, a synthetic cancer nanovaccine platform (nanoSTING-vax) was developed that mimics immunogenic cancer cells in its capacity to efficiently promote co-delivery of peptide antigens and the STING agonist, cGAMP. The co-loading of cGAMP and peptides into pH-responsive, endosomolytic polymersomes promoted the coordinated delivery of both cGAMP and peptide antigens to the cytosol, thereby eliciting inflammatory cytokine production, costimulatory marker expression, and antigen cross-presentation. Consequently, nanoSTING-vax significantly enhanced CD8+ T cell responses to a range of peptide antigens. Therapeutic immunization with nanoSTING-vax, in combination with immune checkpoint blockade, inhibited tumor growth in multiple murine tumor models, even leading to complete tumor rejection and generation of durable antitumor immune memory. Collectively, this work establishes nanoSTING-vax as a versatile platform for enhancing immune responses to neoantigen-targeted cancer vaccines.
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DOI：
10.4049/jimmunol.1601629
发表时间：
2017-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Audiger C;Rahman MJ;Yun TJ;Tarbell KV;Lesage S
通讯作者：
Lesage S
影响因子：
4.9
作者：
Collier MA;Junkins RD;Gallovic MD;Johnson BM;Johnson MM;Macintyre AN;Sempowski GD;Bachelder EM;Ting JP;Ainslie KM
通讯作者：
Ainslie KM
影响因子：
15.9
作者：
Hanson, Melissa C.;Crespo, Monica R.;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
5.2
作者：
Gaffney, Barbara L.;Veliath, Elizabeth;Zhao, Jianwei;Jones, Roger A.
通讯作者：
Jones, Roger A.