Ionizable polymeric nanocarriers for the codelivery of bi-adjuvant and neoantigens in combination tumor immunotherapy.
Ionizable polymeric nanocarriers for the codelivery of bi-adjuvant and neoantigens in combination tumor immunotherapy.
复制标题
DOI：
10.1016/j.bioactmat.2023.02.016
复制
发表时间：
2023-08
影响因子：
18.9
通讯作者：
Zhu, Guizhi
中科院分区：
文献类型：
--
作者：
Su, Ting;Liu, Xiang;Lin, Shuibin;Cheng, Furong;Zhu, Guizhi
关键词：
可电离脂质纳米载体为COVID-19 mRNA疫苗做出了历史性贡献。在这里，我们报道了可电离的聚合物纳米颗粒，联合免疫检查点阻断（ICB），共同递送双佐剂和新抗原肽用于癌症免疫治疗。目前的癌症ICB仅使一小部分患者受益，主要是由于缺乏预先存在的ICB靶细胞和检查点靶点，肿瘤抗原异质性和肿瘤免疫抑制。治疗性疫苗有可能通过扩大抗肿瘤细胞库、上调免疫检查点水平从而使ICB增敏和减少肿瘤免疫抑制来增强ICB的治疗效果。化学定义的肽疫苗很有吸引力，但其目前的治疗效果受到以下因素的限制：1)疫苗递送到免疫调节淋巴结（LNs）和抗原（Ag）呈递细胞（APCs）的效果较差；2)免疫刺激剂佐剂在人类有限靶细胞亚群中的效果较差；3)佐剂/Ag共递送以增强Ag免疫原性的能力有限；4)克服肿瘤抗原异质性的能力有限。在这里，我们开发了使用ph反应性聚合物微细胞纳米颗粒（NPs）的纳米疫苗（NVs），用于将双佐剂[toll样受体（TLR） 7/8激动剂R848和TLR9激动剂CpG]和肽新抗原（neoAgs）共同递送到引流LNs中，以便在广泛的APC亚群中有效地呈递Ag。这些NVs增强了肽Ags的免疫原性，引发了具有记忆的强大的抗肿瘤T细胞反应，并通过减少肿瘤免疫抑制来重塑肿瘤免疫细胞。结果表明，NVs显著增强了ICB对小鼠结直肠肿瘤和原位多形性胶质母细胞瘤（GBM）的治疗效果。这些结果表明双佐剂/ neoag共递送NVs用于联合癌症免疫治疗的显著潜力。我们开发了纳米疫苗，共同递送双佐剂和新抗原，以增强抗肿瘤免疫和肿瘤免疫治疗。通过记忆诱发强大的抗肿瘤T细胞反应，并重塑肿瘤免疫细胞。增强对小鼠结直肠肿瘤和原位多形性胶质母细胞瘤的联合治疗效果。
Ionizable lipid nanocarriers have made historical contribution to COVID-19 mRNA vaccines. Here, we report ionizable polymeric nanoparticles that co-deliver bi-adjuvant and neoantigen peptides for cancer immunotherapy in combination with immune checkpoint blockade (ICB). Current cancer ICB benefits only a small subset of patients, largely due to a lack of pre-existing target cells and checkpoint targets for ICB, tumor antigenic heterogeneity, and tumor immunosuppression. Therapeutic vaccines hold the potential to enhance ICB therapeutic efficacy by expanding antitumor cell repertoires, upregulating immune checkpoint levels and hence sensitizing ICB, and reducing tumor immunosuppression. Chemically defined peptide vaccines are attractive, but their current therapeutic efficacy has been limited due to 1) poor vaccine delivery to immunomodulatory lymph nodes (LNs) and antigen (Ag)-presenting cells (APCs), 2) poor immunostimulant adjuvant efficacy with restricted target cell subsets in humans, 3) limited adjuvant/Ag codelivery to enhance Ag immunogenicity, and 4) limited ability to overcome tumor antigenic heterogeneity. Here, we developed nanovaccines (NVs) using pH-responsive polymeric micellular nanoparticles (NPs) for the codelivery of bi-adjuvant [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] and peptide neoantigens (neoAgs) to draining LNs for efficient Ag presentation in a broad range of APC subsets. These NVs potentiated the immunogenicity of peptide Ags and elicits robust antitumor T cell responses with memory, and remodeled the tumor immune milium with reduced tumor immunosuppression. As a result, NVs significantly enhanced ICB therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme (GBM). These results suggest marked potential of bi-adjuvant/neoAg-codelivering NVs for combination cancer immunotherapy. We developed nanovaccines that codeliver bi-adjuvant and neoantigen to potentiate antitumor immunity and tumor immunotherapy. potentiate elicit robust antitumor T cell responses with memory, and remodel the tumor immune milium. Enhanced the combination therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme.
登录
查看更多内容
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
15.9
作者：
Cohen, Cyrille J.;Gartner, Jared J.;Robbins, Paul F.
通讯作者：
Robbins, Paul F.
影响因子：
5.6
作者：
Hu, Zhengran;Wang, Feifan;Li, Min
通讯作者：
Li, Min
癌症免疫疗法。树突状细胞疫苗增加了黑色素瘤新抗原特异性T细胞的广度和多样性。
DOI：
10.1126/science.aaa3828
发表时间：
2015-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carreno BM;Magrini V;Becker-Hapak M;Kaabinejadian S;Hundal J;Petti AA;Ly A;Lie WR;Hildebrand WH;Mardis ER;Linette GP
通讯作者：
Linette GP
影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS