Project 1: Optimizing a VSV-based virotherapy-based regimen for advanced MM
Project 1: Optimizing a VSV-based virotherapy-based regimen for advanced MM
批准号:
10488659
负责人:
MARTHA Q LACY
金额:
$34.89万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
未结题
起止时间:
2015-09-01 至 2026-08-31
关键词:
AntibodiesAntibody TherapyAntibody titer measurementCell DeathCellsClinicClinicalCyclophosphamideCytolysisCytotoxic T-LymphocytesDataDisease remissionDoseEngineeringFrequenciesFundingGene Expression ProfileGoalsGrantHematologic NeoplasmsHourImmuneImmune responseImmune systemImmunomodulatorsImmunosuppressionInfectionInflammationInflammation MediatorsInflammatoryInfusion proceduresInterferon-betaInterferonsIntravenousIntravenous infusion proceduresKineticsLymphomaMeasuresMediatingModalityModelingMonitorMultiple MyelomaMutationNormal tissue morphologyOncolyticPatientsPharmaceutical PreparationsPhasePhase II Clinical TrialsPhase Ib Clinical TrialPositron-Emission TomographyRadiation therapyRegimenRegulatory T-LymphocyteResearch PersonnelSLC5A5 geneSafetySalivaSeroprevalencesSerumSignal TransductionSpecificitySystemic TherapyT cell responseT-Cell LymphomaT-LymphocyteTestingTherapeuticToxic effectTracerTumor AntigensUrineVesicular stomatitis Indiana virusViralViral GenomeViremiaVirotherapyVirusVirus Diseasesanti-PD-1anti-PD1 antibodiesanti-tumor immune responsebasecancer therapycell killingexhaustionexomefirst-in-humanhuman studyimmune checkpoint blockademouse modelneoantigensneoplastic cellnoveloncolytic Vesicular Stomatitis Virusoncolytic virotherapypharmacodynamic biomarkerpharmacokinetics and pharmacodynamicspre-clinicalresponsetherapy outcometranscriptome sequencingtumor
中文摘要
项目摘要
溶瘤病毒疗法是一种两阶段疗法。在溶瘤期(短暂),感染在
肿瘤,杀死受感染的细胞和发炎的微环境。在免疫阶段(延长)引发和
通过炎症介质和吞噬碎片扩增肿瘤特异性细胞毒性T细胞(CTL)
死亡或垂死的肿瘤细胞导致未感染的肿瘤细胞被杀死。VSV-IFNβ-NIS是一种快速复制的
溶瘤性水泡性口炎病毒(VSV),其导致炎性肿瘤细胞杀伤。在第一次骨髓瘤
在SPORE资助期间,我们启动了一项由研究者发起的单剂量、单药物的首次人体研究。
静脉内(IV)VSV-IFNβ-NIS治疗恶性血液病患者。具有良好的耐受性,
令人鼓舞的抗肿瘤活性迹象。进行了广泛的相关分析,以表征
抗肿瘤免疫应答的动力学及其与患者特异性基线参数的关系。
在第二个骨髓瘤孢子资助期间,我们寻求最大限度地提高静脉注射的效力。
通过联合(i)重复病毒给药,(ii)早期抑制抗病毒药物,
免疫反应,以及(iii)通过使用免疫抑制组合来晚期加强抗骨髓瘤T细胞
和免疫激活方案,总体目标是使用VSV病毒疗法在
多发性骨髓瘤患者。
英文摘要
PROJECT SUMMARY
Oncolytic virotherapy is a two-stage therapy. In the oncolytic phase (short-lived) the infection spreads in the
tumor, killing infected cells and inflaming the microenvironment. In the immune phase (prolonged) priming and
amplification of tumor-specific cytotoxic T cells (CTLs) by inflammatory mediators and phagocytosed debris
from dead or dying tumor cells leads to killing of uninfected tumor cells. VSV-IFNβ-NIS is a fast-replicating
oncolytic Vesicular Stomatitis Virus (VSV) that causes inflammatory tumor cell killing. During the first Myeloma
SPORE funding period, we launched an investigator initiated first-in-human study of single dose, single agent
intravenous (IV) VSV-IFNβ-NIS in patients with hematological malignancies. There is good tolerability and
encouraging signs of antitumor activity. Extensive correlative analyses have been conducted to characterize
the kinetics of the antitumor immune responses, and their relationship to patient-specific baseline parameters.
During the second Myeloma SPORE funding period we seek to maximize the potency of intravenous
VSVIFNβ-NIS therapy by combining (i) repeat virus administration, (ii) early suppression of the antiviral
immune response, and (iii) late boosting of antimyeloma T cells by using a combination of immune suppression
and immune activating regimens with the overall goal to achieve a durable response using VSV virotherapy in
patients with multiple myeloma.
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Project 1: Optimizing a VSV-based virotherapy-based regimen for advanced MM
-
批准号:10270455
-
项目类别:
-
资助金额:$29.67万
-
财政年份:2015
-
负责人:MARTHA Q LACY
-
依托单位:
Dendritic Cell-Based Idiotype Vaccination with INF/IL2
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批准号:7042286
-
项目类别:
-
资助金额:$0.19万
-
财政年份:2003
-
负责人:MARTHA Q LACY
-
依托单位:
Dendritic Cell Based Vaccination with Idiotype for Amyloidosis
-
批准号:7042247
-
项目类别:
-
资助金额:$0.12万
-
财政年份:2003
-
负责人:MARTHA Q LACY
-
依托单位:
DENDRITIC CELL BASED VACCINATION W/ IDIOTYPE FOR AMYLOIDOSIS & POST TRANSPLANT
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批准号:6265003
-
项目类别:
-
资助金额:$2.01万
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财政年份:1998
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负责人:MARTHA Q LACY
-
依托单位:
海外基金