Develop a Therapeutic Nano-vaccine against Head and Neck Cancer
开发针对头颈癌的治疗性纳米疫苗
基本信息
- 批准号:10372999
- 负责人:
- 金额:$ 36.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAntigen-Presenting CellsAntigensAutophagocytosisBedsBiomedical EngineeringBlocking AntibodiesCancer DetectionCancer PatientCell LineCell ProliferationCellsCellular biologyClinicalCross-PrimingCytotoxic T-LymphocytesDefectDeglutitionDetectionDisease ProgressionEffector CellEngineeringExhibitsFailureGenerationsGenesGoalsHalf-LifeHead and Neck CancerHead and Neck Squamous Cell CarcinomaHomingHumanHuman PapillomavirusImmuneImmune ToleranceImmune checkpoint inhibitorImmunityImmunologyImmunotherapyImplantIn VitroInfiltrationInterferon Type IInterferon-betaInterferonsJawLockjawLymphocyte FunctionMalignant NeoplasmsMediatingModelingMonoclonal AntibodiesMorbidity - disease rateMycosesNeoadjuvant TherapyOncogenesOralPathway interactionsPatientsPrognosisRegimenResistanceResistance developmentRoleSTING agonistsSignal TransductionSting InjurySurgical ManagementSystemT-LymphocyteTechnologyTestingTissue MicroarrayTumor AntigensTumor BurdenTumor ExpansionTumor ImmunityTumor-Infiltrating LymphocytesTumor-infiltrating immune cellsVaccinesXerostomiaadaptive immunityanti-tumor immune responseantigen-specific T cellsbiomaterial compatibilitybonecancer cellcheckpoint receptorschemoradiationcytotoxic CD8 T cellscytotoxicitydensityefficacy evaluationexhaustfollow-uphead and neck cancer patientimmune activationimmune checkpointimmune checkpoint blockadeimmunogenicimmunogenicityimproved functioningin vivoinnovationmalignant mouth neoplasmnanotherapeuticnanovaccineneoantigensneoplastic cellnovel strategiespatient subsetsprototypepublic health relevancereceptorresistance mechanismresponsestemsuccesstargeted treatmenttraffickingtranscriptome sequencingtumortumor growthtumor microenvironmenttumor-immune system interactionsvaccine efficacy
项目摘要
PROJECT SUMMARY
Clinical success of immune checkpoint receptor (ICR) blockade stems from its efficacy in restoring the
effector function of exhausted tumor-infiltrating lymphocytes. But an exclusive effector immune cell-targeted
treatment is prone to failure in hypoimmunogenic cold tumors, which are featured by insufficient elicitation of
tumor-specific T-cell immunity and resistance to immunogenic cytotoxicity. Indeed, about 80% of Oral, Head &
Neck Squamous Cell Carcinoma (HNC) patients do not respond to ICR blockade. Conventional
chemoradiotherapy and surgical management are associated with high morbidity, such as swallowing
problems, dry mouth, fungal infection, dead bone of the jaw, disfigurement, and “lock-jaw”. Deescalating
treatment results in disease progression. Thus, it is urgent to characterize the mechanisms underpinning HNC
hypoimmunogenicity. Our preliminary study identifies type I interferon signaling in the tumor microenvironment
as a key pathway modulating the plasticity of anti-tumor immune response. Type I interferon target genes
promote antigen-presenting cell (APC) and effector cell trafficking to the tumor bed, and enhance APC cross-
priming efficiency. To mitigate the negative impact of cold HNC upon immune activation, we engineered a
nano-vaccine system that potently enhances type I interferon signaling and antigen delivery. Our prototype
nano-vaccine leads to an over 12-fold expansion of tumor-specific T cells in the tumor microenvironment, and
significantly reduces tumor burden. Informed by our results and in response to the FOA, the overarching
hypothesis of the project is: type I interferon signaling is essential to maintain HNC immunogenicity, and our
nano-vaccine sensitizes cold HNC to ICR blockade. To test this hypothesis, three aims are put in place: **(1)
we will characterize the role of type I interferon signaling in modulating HNC immunogenicity; **(2) we will
determine the mechanisms HNC cells employ to dampen type I interferon signaling and promote resistance to
checkpoint blockade; **(3) we will optimize a type I interferon-inducing tumor-specific nano-vaccine system to
break HNC immune tolerance. These goals are in precise alignment with the FOA. (1) We will elucidate the
role of type I interferon signaling in modulating the plasticity of anti-tumor immunity. (2) We will develop a safe,
biocompatible, highly immunogenic and effective nano-vaccine technology to precisely and predictably enrich
tumor antigen-specific T-cell repertoire.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Yu Leo Lei其他文献
IL-1α Mediated Suppressive Myeloid Function in Head and Neck Cancer
IL-1α 介导的头颈癌抑制性骨髓功能
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Hulya F. Taner;Wang Gong;Kohei Okuyama;Luke Proses;Wanqing Cheng;Jung Kuczura;Sashider Rajesh;Yuying Xie;Yu Leo Lei - 通讯作者:
Yu Leo Lei
Localized intratumoral delivery of immunomodulators for oral cancer and oral potentially malignant disorders
免疫调节剂口腔癌和口腔潜在恶性疾病的局部肿瘤内输送
- DOI:
10.1016/j.oraloncology.2024.106986 - 发表时间:
2024-11-01 - 期刊:
- 影响因子:3.900
- 作者:
Nourhan I. Hussein;Andrea H. Molina;Gemalene M. Sunga;Moran Amit;Yu Leo Lei;Xiao Zhao;Jeffrey D. Hartgerink;Andrew G. Sikora;Simon Young - 通讯作者:
Simon Young
Resolving an Immune Tolerogenic Niche at the Earliest Phase of Oral Cancer Initiation
在口腔癌发生的最早阶段解决免疫耐受性生态位
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Hulya Taner;Wang Gong;Luke Broses;Kohei Okuyama;Wanqing Cheng;Jung Kuczura;Sashider Rajesh;Yee Sun Tan;Shadmehr Demehri;Jianwen Que;Yuying Xie;Yu Leo Lei - 通讯作者:
Yu Leo Lei
Sox2-driven Epithelial Transformation Promotes IL1-mediated Peripheral Immune Tolerance
Sox2 驱动的上皮转化促进 IL1 介导的外周免疫耐受
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Hulya F. Taner;Wang Gong;Kohei Okuyama;Luke Broses;Wanqing Cheng;Jung Kuczura;Sashider Rajesh;Yuying Xie;Yu Leo Lei - 通讯作者:
Yu Leo Lei
BATF2 suppresses cancer initiation by promoting γδ T-cell-mediated immunity
BATF2 通过促进 γδ T 细胞介导的免疫来抑制癌症发生
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Wang Gong;Hulya Taner;Yuesong Wu;Wanqing Cheng;Kohei Okuyama;Zaiye Li;Shadmehr Demehri;Felipe Nor;Deepak Nagrath;Steven B Chinn;Christopher R Donnelly;James J Moon;Yuying Xie;Yu Leo Lei - 通讯作者:
Yu Leo Lei
Yu Leo Lei的其他文献
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{{ truncateString('Yu Leo Lei', 18)}}的其他基金
Engineered Nano-formulations for STING Activation
用于 STING 激活的工程纳米制剂
- 批准号:
10539415 - 财政年份:2022
- 资助金额:
$ 36.68万 - 项目类别:
Engineered Nano-formulations for STING Activation
用于 STING 激活的工程纳米制剂
- 批准号:
10661091 - 财政年份:2022
- 资助金额:
$ 36.68万 - 项目类别:
New Engineering Strategy for Harnessing Immune System against Head and Neck Cancer
利用免疫系统对抗头颈癌的新工程策略
- 批准号:
10316349 - 财政年份:2021
- 资助金额:
$ 36.68万 - 项目类别:
New Engineering Strategy for Harnessing Immune System against Head and Neck Cancer
利用免疫系统对抗头颈癌的新工程策略
- 批准号:
10615115 - 财政年份:2021
- 资助金额:
$ 36.68万 - 项目类别:
New Engineering Strategy for Harnessing Immune System against Head and Neck Cancer
利用免疫系统对抗头颈癌的新工程策略
- 批准号:
10434134 - 财政年份:2021
- 资助金额:
$ 36.68万 - 项目类别:
Restoring the Immunogenicity of Head and Neck Cancer
恢复头颈癌的免疫原性
- 批准号:
10732281 - 财政年份:2018
- 资助金额:
$ 36.68万 - 项目类别:
Develop a Therapeutic Nano-vaccine against Head and Neck Cancer
开发针对头颈癌的治疗性纳米疫苗
- 批准号:
9895433 - 财政年份:2018
- 资助金额:
$ 36.68万 - 项目类别:
Development of a Prognostic Compound Immunoscore for Head and Neck Cancer
头颈癌预后复合免疫评分的开发
- 批准号:
9766266 - 财政年份:2018
- 资助金额:
$ 36.68万 - 项目类别:
Autophagy-promoting NLRX1-TUFM complex and cancer cell resistance to cetuximab
促进自噬的NLRX1-TUFM复合物和癌细胞对西妥昔单抗的耐药性
- 批准号:
8923237 - 财政年份:2014
- 资助金额:
$ 36.68万 - 项目类别:
Autophagy-promoting NLRX1-TUFM complex and cancer cell resistance to cetuximab
促进自噬的NLRX1-TUFM复合物和癌细胞对西妥昔单抗的耐药性
- 批准号:
9464986 - 财政年份:2014
- 资助金额:
$ 36.68万 - 项目类别:
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