mRNA encoding of immune receptor-targeting antibodies for the augmentation of vaccine-elicited cellular immunity.
编码免疫受体靶向抗体的 mRNA,用于增强疫苗引发的细胞免疫。
基本信息
- 批准号:10662571
- 负责人:
- 金额:$ 19.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-08 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAdjuvant StudyAdmission activityAgonistAnti-CD40AntibodiesAntibody FormationAntibody ResponseAntigensAreaCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCOVID-19COVID-19 vaccineCTLA4 geneCellsCellular ImmunityChronicClinicalCommunicable DiseasesDataDevelopmentEncapsulatedEngineeringFDA approvedFormulationFrequenciesGenesGoalsHumoral ImmunitiesImmuneImmune TargetingImmune responseImmune systemImmunityImmunizationImmunologic ReceptorsImmunologicsImmunotherapeutic agentIndividualInfectionInterferon Type IInterventionIntravenous infusion proceduresLifeLightLipidsMalignant NeoplasmsMeasuresMediatingMemoryMessenger RNAMethodsModelingMolecular TargetMonoclonal AntibodiesMusNatureOncologyPathway interactionsPatientsPhenotypeQualitative EvaluationsRNA vaccinationRNA vaccineResearch Project GrantsSARS-CoV-2 immunitySignal PathwaySignal TransductionSourceStimulusT cell responseT memory cellT-LymphocyteTNFRSF5 geneTechnologyTestingTherapeuticTherapeutic InterventionTranslatingTreatment EfficacyTreatment ProtocolsTumor PromotionVaccinationVaccine AdjuvantVaccinesValidationVariantWorkanti-CTLA4anti-PD-1checkpoint therapychronic infectionclinical applicationclinical implementationclinically relevantcostexperimental studyimmune checkpoint blockadein vivolipid nanoparticlemRNA deliverymanufacturenanoparticlenonhuman primatepandemic diseaseparticleprogrammed cell death protein 1protein purificationresearch clinical testingresponsesingle-cell RNA sequencingstem cellssuccesstherapeutic targettumorvaccination strategyvaccine deliveryvaccine platformvaccine-induced immunityviral transmission
项目摘要
Project summary.
Clinically relevant cellular responses to either experimental or FDA approved vaccine adjuvant formulations
have been difficult to generate and/or detect. We have long been investigating a combined adjuvant
formulation (composed of a TLR agonist and an agonistic antiCD40 antibody) which generates cellular
immunity on par with that observed to infectious challenge. The complexity of this three-part vaccine (antigen
plus TLR/CD40) is limiting to its clinical application. However, the success of lipid nanoparticle (LNP)
encapsulated mRNA vaccines for Covid provides a possible avenue by which our combination adjuvant might
be successfully translated into clinical use against chronic infectious diseases and cancer. Our preliminary
results show that we can agonize the CD40 pathway, sufficient to augment CD8 T cell responses, by mRNA-
mediated delivery of the heavy and light chains of the agonistic anti-CD40 antibody FGK45. The success of
this method for targeting CD40 strongly favors the hypothesis that antibodies specific for other
immunotherapeutic molecular targets (eg. CTLA4, PD1) might also be successfully delivered via the mRNA
vaccination strategy. Completion of this project would not only identify a new and powerful means by which
the established potency of our combined adjuvant might be leveraged for clinical application, they open an
entirely new paradigm in the use of mRNA vaccination for targeting immunologically relevant molecules for the
purposes oncologic checkpoint therapy and beyond.
项目总结。
对实验性或FDA批准的疫苗佐剂制剂的临床相关细胞反应
已经很难生成和/或检测。我们一直在研究一种联合佐剂
制剂(由TLR激动剂和激动型抗CD40抗体组成)可产生细胞
免疫力与观察到的对感染性攻击的免疫力相当。这种三部分疫苗(抗原)的复杂性
加上TLR/CD40)限制了其临床应用。然而,脂质纳米粒(LNP)的成功
Covid的微囊化mRNA疫苗为我们的联合佐剂提供了一条可能的途径
成功地转化为治疗慢性传染病和癌症的临床应用。我们的预赛
结果表明,我们可以激动CD40途径,足以增强CD8T细胞的反应,通过mRNA-
介导的激动型抗CD40抗体FGK45的重链和轻链的传递。的成功之处
这种以CD40为靶点的方法强烈支持这样的假设,即针对其他
免疫治疗分子靶点(如CTLA4,PD1)也可能通过mRNA成功传递
疫苗接种策略。该项目的完成不仅将确定一种新的和强大的手段,通过
我们联合佐剂的既定效力可能会被用于临床应用,他们打开了一个
使用信使核糖核酸疫苗靶向免疫相关分子治疗的全新范例
目的:肿瘤学检查点治疗及其他。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Ross M Kedl其他文献
Ross M Kedl的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Ross M Kedl', 18)}}的其他基金
mRNA encoding of immune receptor-targeting antibodies for the augmentation of vaccine-elicited cellular immunity.
编码免疫受体靶向抗体的 mRNA,用于增强疫苗引发的细胞免疫。
- 批准号:
10508093 - 财政年份:2022
- 资助金额:
$ 19.44万 - 项目类别:
Exploring the heterogeneity of the vaccine-elicited T cell response by scRNAseq
通过 scRNAseq 探索疫苗引发的 T 细胞反应的异质性
- 批准号:
10334559 - 财政年份:2021
- 资助金额:
$ 19.44万 - 项目类别:
Exploring the heterogeneity of the vaccine-elicited T cell response by scRNAseq
通过 scRNAseq 探索疫苗引发的 T 细胞反应的异质性
- 批准号:
10218805 - 财政年份:2021
- 资助金额:
$ 19.44万 - 项目类别:
CD8 T cell and B cell collaboration following subunit vaccination
亚单位疫苗接种后 CD8 T 细胞和 B 细胞协作
- 批准号:
10450847 - 财政年份:2020
- 资助金额:
$ 19.44万 - 项目类别:
CD8 T cell and B cell collaboration following subunit vaccination
亚单位疫苗接种后 CD8 T 细胞和 B 细胞协作
- 批准号:
10662244 - 财政年份:2020
- 资助金额:
$ 19.44万 - 项目类别:
CD8 T cell and B cell collaboration following subunit vaccination
亚单位疫苗接种后 CD8 T 细胞和 B 细胞协作
- 批准号:
10055979 - 财政年份:2020
- 资助金额:
$ 19.44万 - 项目类别:
CD8 T cell and B cell collaboration following subunit vaccination
亚单位疫苗接种后 CD8 T 细胞和 B 细胞协作
- 批准号:
10242218 - 财政年份:2020
- 资助金额:
$ 19.44万 - 项目类别:
Molecular and cellular basis of Combined Adjuvant-Elicited Cellular Immunity
联合佐剂引发的细胞免疫的分子和细胞基础
- 批准号:
9312770 - 财政年份:2016
- 资助金额:
$ 19.44万 - 项目类别:
Molecular and cellular basis of Combined Adjuvant-Elicited Cellular Immunity
联合佐剂引发的细胞免疫的分子和细胞基础
- 批准号:
9197094 - 财政年份:2016
- 资助金额:
$ 19.44万 - 项目类别:
Lymphatic endothelial cell capture and maintenance of antigen
淋巴内皮细胞捕获和维持抗原
- 批准号:
8895716 - 财政年份:2015
- 资助金额:
$ 19.44万 - 项目类别: