Engineering Nanomaterials to Prime Immunity

工程纳米材料增强免疫力

• 批准号: 10063848
• 负责人: James J Moon
• 金额: $ 41.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063848
• 关键词: Address; Adjuvant; Affect; Animals; Antibody Response; Antigen Presentation; Antigen Presentation Pathway; Antigens; B-Lymphocytes; Benchmarking; Biomedical Engineering; CD8-Positive T-Lymphocytes; Cancer Vaccines; Characteristics; Clinical Trials; Combined Vaccines; Cross Presentation; Cross-Priming; Data; Dendritic Cells; Development; Engineering; Exhibits; Formulation; Generations; Goals; Gold; Human; Immune checkpoint inhibitor; Immune response; Immunity; Immunization; Immunoglobulin G; Immunologics; Immunology; Immunosuppression; Immunotherapy; Knowledge; Lead; Lipase; Lipids; Malignant Neoplasms; Mediating; Melanoma Vaccine; Metastatic Melanoma; Modeling; Mus; Mutate; Nanotechnology; Oils; Outcome; Predisposition; Property; Public Health; Research; Series; Serum; System; T cell response; T-Lymphocyte; Technology; Testing; Therapeutic; Therapeutic Effect; Treatment Efficacy; Tumor Antigens; Tumor Immunity; Tumor-infiltrating immune cells; Vaccination; Vaccines; Vesicle; Water; anti-PD1 therapy; anti-tumor immune response; antitumor effect; base; biomaterial compatibility; cancer immunotherapy; crosslink; cytotoxic CD8 T cells; design; draining lymph node; effective therapy; exome sequencing; immune activation; immune checkpoint blockade; improved; in vivo; innovation; materials science; melanoma; mouse model; nanoformulation; nanomaterials; nanoparticle; nanosystems; nanovaccine; neoantigens; next generation; novel; novel vaccines; personalized immunotherapy; programmed cell death protein 1; receptor; response; therapy design; trafficking; tumor; tumor exome; tumor microenvironment; vaccine development; vaccine efficacy

Abstract Development of vaccine technologies with therapeutic efficacy against cancer has been an elusive goal. Conventional adjuvants induce weak levels of cytotoxic CD8+ T lymphocyte (CTL) responses, while accumulating evidence suggests that simultaneous CTL and antibody (Ab) responses are needed for effective therapy. Therefore, there is a critical need for alternative approaches that can achieve strong anti-tumor immune responses. Our long-term research goal is to develop new material-based strategies that can achieve immune stimulation with potent therapeutic efficacy against cancer. Our objective in this R01 application is to delineate the key nanomaterial criteria for designing effective nano-vaccines and to utilize knowledge gained from these studies to develop a powerful vaccine technology for treatment of primary and metastatic melanomas. To that end, we have developed a novel nano-vaccine system that can (a) efficiently transport antigen (Ag) to dendritic cells (DCs); (b) promote Ag cross-presentation and cross-priming of T-cells; (c) generate significantly stronger Ag-specific CD8+ T-cell responses than conventional vaccines based on DCs, other nano-formulations, and experimental adjuvants in clinical trials; (d) enhance accumulation of anti-tumor T-cells in tumor microenvironment; and (e) induce anti-tumor immunity against primary and metastatic melanomas, in a biocompatible and safe manner. In this application, we propose to address the following questions: what are unique characteristics of our nano-vaccines that evoke such strong anti-tumor immunity, compared with other traditional cancer vaccines? Can we in turn modulate these parameters to further optimize our nano-vaccine technology and amplify anti-tumor immunity? We will evaluate outcomes of our strategy in murine models of locally and systemically disseminated melanomas. Our innovative approach employing interdisciplinary principles of materials science, bioengineering, and immunology will lead to a new vaccine nanotechnology that may eliminate primary and metastatic melanomas and improve cancer immunotherapy.

抽象的 开发具有抗癌功效的疫苗技术一直是一个难以实现的目标。 传统佐剂诱导微弱水平的细胞毒性 CD8+ T 淋巴细胞 (CTL) 反应，而 越来越多的证据表明，需要同时进行 CTL 和抗体 (Ab) 反应才能有效 治疗。因此，迫切需要能够实现强效抗肿瘤的替代方法 免疫反应。我们的长期研究目标是开发新的基于材料的策略，以实现 免疫刺激对癌症具有强大的治疗功效。我们在此 R01 应用程序中的目标是 描述设计有效纳米疫苗的关键纳米材料标准并利用所获得的知识 从这些研究中开发出一种强大的疫苗技术来治疗原发性和转移性癌症 黑色素瘤。为此，我们开发了一种新型纳米疫苗系统，它可以（a）有效地运输 树突状细胞 (DC) 抗原 (Ag)； (b) 促进 T 细胞的 Ag 交叉呈递和交叉启动； (三) 与基于 DC 的传统疫苗相比，产生明显更强的 Ag 特异性 CD8+ T 细胞反应， 其他纳米制剂以及临床试验中的实验佐剂； (d)增强抗肿瘤积累 肿瘤微环境中的T细胞； (e) 诱导针对原发性和转移性肿瘤的抗肿瘤免疫 黑色素瘤，以生物相容性和安全的方式。在本申请中，我们建议解决以下问题 问题：我们的纳米疫苗有哪些独特的特性可以激发如此强大的抗肿瘤免疫力， 与其他传统癌症疫苗相比？我们能否依次调节这些参数以进一步 优化我们的纳米疫苗技术，增强抗肿瘤免疫力？我们将评估我们的成果 局部和全身播散性黑色素瘤小鼠模型的策略。我们的创新方法 采用材料科学、生物工程和免疫学的跨学科原理将产生新的 疫苗纳米技术可以消除原发性和转移性黑色素瘤并改善癌症 免疫疗法。

项目成果

Immunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy.

癌症免疫治疗的共定位佐剂递送放大了免疫原性细胞死亡。

• DOI: 10.1021/acs.nanolett.7b03218
• 发表时间: 2017-12-13
• 期刊: Nano letters
• 影响因子: 10.8
• 作者: Fan Y;Kuai R;Xu Y;Ochyl LJ;Irvine DJ;Moon JJ
• 通讯作者: Moon JJ

High-density lipoprotein-mimicking nanodiscs carrying peptide for enhanced therapeutic angiogenesis in diabetic hindlimb ischemia.

• DOI: 10.1016/j.biomaterials.2018.01.027
• 发表时间: 2018-04
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Park HJ;Kuai R;Jeon EJ;Seo Y;Jung Y;Moon JJ;Schwendeman A;Cho SW
• 通讯作者: Cho SW

Non-viral COVID-19 vaccine delivery systems.

非病毒Covid-19疫苗输送系统。

• DOI: 10.1016/j.addr.2020.12.008
• 发表时间: 2021-03
• 期刊: Advanced drug delivery reviews
• 影响因子: 16.1
• 作者: Park KS;Sun X;Aikins ME;Moon JJ
• 通讯作者: Moon JJ

Engineering Strategies to Modulate the Gut Microbiome and Immune System.

• DOI: 10.4049/jimmunol.2300480
• 发表时间: 2024-01
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: Kai Han;Jin Xu;Fang Xie;Julia Crowther;James J Moon

Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy.

• DOI: 10.1016/j.jconrel.2018.04.041
• 发表时间: 2018-07-28
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Kuai R;Sun X;Yuan W;Ochyl LJ;Xu Y;Hassani Najafabadi A;Scheetz L;Yu MZ;Balwani I;Schwendeman A;Moon JJ
• 通讯作者: Moon JJ