Synergy between BRAF inhibition, tumor-localized T cells and a persistent vaccine
BRAF 抑制、肿瘤定位 T 细胞和持久性疫苗之间的协同作用
基本信息
- 批准号:8635992
- 负责人:
- 金额:$ 7.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-04-01 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAffectAllelesAntibodiesAntigensApplications GrantsBRAF geneBlocking AntibodiesCancer VaccinesCell physiologyCellsClinicClinical TrialsCytomegalovirusDataDevelopmentDiseaseEconomic InflationEnvironmentFDA approvedFailureFunctional disorderGenerationsGenomeGoalsHerpesviridaeHumanImmuneImmune responseImmune systemImmunityImmunosuppressionImmunotherapyIn VitroInfiltrationLungLyticMaintenanceMalignant NeoplasmsMeasuresMemoryMetastatic MelanomaModelingMusMutateMutationNeoplasm MetastasisOrganPTEN genePathologyPathway interactionsPatientsPatternPenetrancePopulationPrimary NeoplasmProductionProtein-Serine-Threonine KinasesProto-Oncogene Proteins B-rafRecombinantsRouteSignal TransductionSourceT cell responseT-Cell ProliferationT-LymphocyteTestingTimeTumor Suppressor ProteinsVaccinatedVaccinationVaccinesVaccinia virusVariantWorkabstractingbasecell motilitycytokineefficacy testingexhaustionhuman diseaseimmunogenicin vivoinhibitor/antagonistlatent persistent infectionlymph nodesmelanomamigrationmucosal sitemutantneoplastic cellpublic health relevanceresponsesuccesstraffickingtumortumor progressionvaccination strategyvaccine evaluationvectorvector vaccinevector-based vaccine
项目摘要
DESCRIPTION (provided by applicant): Abstract: A long-standing goal for melanoma immune therapy is the induction of tumor-specific T cells that effectively delay tumor progression and prolong overall patient survival. Several vaccination strategies have been attempted without success, despite often stimulating large numbers of tumor-specific T cells. Some of this failure is
likely due to the active immune suppression mechanisms that operate within tumors. Moreover, it has become apparent that T cell trafficking and migration into tumors will be heavily influenced
by the conditions in which those T cells were stimulated. Thus, the ideal cancer vaccine would overcome the immune suppressive environment of the tumor and produce cells that readily migrate into the primary tumor and metastases, wherever they may be. We argue here that a persistent vaccine vector, based on a spread- defective version of the herpes virus cytomegalovirus (CMV), may overcome some of these obstacles. Specifically, persistent CMV-based vectors will continuously boost the immune system outside of the tumor environment and produce T cells that are highly effective at migrating systemically. Our previous work demonstrated that a safe, spread-defective variant of CMV could persist and stimulate large T cell responses. Our aim for this small grant application is to determine the potential for (or limitations of) such a vaccine strategy. To accomplish this, we will use a newly generated, highly relevant model of metastatic melanoma: mice in which expression of a mutant BRAF (BRAFV600E) is induced. BRAF is a serine/threonine kinase that is mutated in ~50% of human melanomas and the BRAFV600E mutation is present in ~80 to 90% of human BRAF-mutant melanomas. Thus, this model mimics human disease. Most excitingly, this model enables us to combine BRAF inhibition with vaccination. This is a great advantage important because BRAF inhibitors, such as the recently FDA approved Vemurafenib, will be widely used in the clinic and recent data suggest that Vemurafenib may synergize with immune therapies. Here we will test the efficacy of CMV-based vaccination in the presence or absence of Vemurafenib inhibition of BRAF, with specific focus on T cell infiltration of tumors and function within tumors.
摘要:黑色素瘤免疫治疗的长期目标是诱导肿瘤特异性T细胞,有效延缓肿瘤进展并延长患者的总体生存期。尽管经常刺激大量肿瘤特异性T细胞,但已经尝试了几种疫苗接种策略,但没有成功。有些失败是
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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Christopher M Snyder其他文献
Christopher M Snyder的其他文献
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{{ truncateString('Christopher M Snyder', 18)}}的其他基金
An animal model for cytomegalovirus-induced pathology in the developing retina
发育中视网膜中巨细胞病毒诱导病理学的动物模型
- 批准号:
10432947 - 财政年份:2022
- 资助金额:
$ 7.52万 - 项目类别:
An animal model for cytomegalovirus-induced pathology in the developing retina
发育中视网膜中巨细胞病毒诱导病理学的动物模型
- 批准号:
10559671 - 财政年份:2022
- 资助金额:
$ 7.52万 - 项目类别:
T cell control of MCMV and tissue-localized immune suppression
T 细胞对 MCMV 的控制和组织局部免疫抑制
- 批准号:
10579272 - 财政年份:2020
- 资助金额:
$ 7.52万 - 项目类别:
T cell control of MCMV and tissue-localized immune suppression
T 细胞对 MCMV 的控制和组织局部免疫抑制
- 批准号:
10348755 - 财政年份:2020
- 资助金额:
$ 7.52万 - 项目类别:
Selection of inflationary and tissue-resident T cells during MCMV infection
MCMV 感染期间膨胀和组织驻留 T 细胞的选择
- 批准号:
8986152 - 财政年份:2014
- 资助金额:
$ 7.52万 - 项目类别:
Selection of inflationary and tissue-resident T cells during MCMV infection
MCMV 感染期间膨胀和组织驻留 T 细胞的选择
- 批准号:
8651139 - 财政年份:2014
- 资助金额:
$ 7.52万 - 项目类别:
Selection of inflationary and tissue-resident T cells during MCMV infection
MCMV 感染期间膨胀和组织驻留 T 细胞的选择
- 批准号:
9198197 - 财政年份:2014
- 资助金额:
$ 7.52万 - 项目类别:
Selection of inflationary and tissue-resident T cells during MCMV infection
MCMV 感染期间膨胀和组织驻留 T 细胞的选择
- 批准号:
8786495 - 财政年份:2014
- 资助金额:
$ 7.52万 - 项目类别:
Selection of inflationary and tissue-resident T cells during MCMV infection
MCMV 感染期间膨胀和组织驻留 T 细胞的选择
- 批准号:
8690204 - 财政年份:2013
- 资助金额:
$ 7.52万 - 项目类别:
Synergy between BRAF inhibition, tumor-localized T cells and a persistent vaccine
BRAF 抑制、肿瘤定位 T 细胞和持久性疫苗之间的协同作用
- 批准号:
8486040 - 财政年份:2013
- 资助金额:
$ 7.52万 - 项目类别:
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