Credentialing a Genetically Engineered Clinically-Relevant Mouse Model of Multiple Myeloma
Credentialing a Genetically Engineered Clinically-Relevant Mouse Model of Multiple Myeloma
批准号:
10053331
负责人:
Marta Chesi
金额:
$37.97万
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
项目状态:
已结题
起止时间:
2018-12-07 至 2023-11-30
关键词:
AddressAmino Acid SequenceAnemiaB-LymphocytesBacterial Artificial ChromosomesBindingBiologicalBiological ModelsBiologyBone DiseasesBone MarrowCell LineCell SurvivalCell TransplantationCellsClinicalCombination Drug TherapyCombined Modality TherapyComplexCredentialingDependenceDrug ReceptorsDrug resistanceDrug usageEngineeringGenerationsGenesGeneticGenetic EngineeringGenomic approachGlucocorticoidsGoalsHematologic NeoplasmsHomeHumanHuman CharacteristicsImmune systemImmunocompetentImmunoglobulin Class SwitchingImmunoglobulin Somatic HypermutationImmunoglobulinsImmunomodulatorsImmunotherapyImpairmentIndolentInterferon Type IIKidneyMediatingModelingMonoclonal gammopathy of uncertain significanceMultiple MyelomaMusMutationNewly DiagnosedPatientsPharmaceutical PreparationsPopulationPre-Clinical ModelPrecancerous ConditionsPredictive ValueProteasome InhibitorPublishingRefractoryRegulatory ElementRelapseResearch PersonnelResistanceRoleSplenocyteStructure of germinal center of lymph nodeT-Cell ProliferationThalidomideTranscription Factor 3Transgenic MiceTransplantationUbiquitinValidationVariantVertebral columnWorkclinical practiceclinical predictorsclinically relevantdrug-sensitiveexperimental studygene productgenetic manipulationhuman diseasein vivoin vivo Modellenalidomidemouse modelneoplasm immunotherapyneoplastic cellnovelplasma cell differentiationpleiotropismpomalidomidepost-transplantreceptorrecruitrelapse patientsresponsetumortumor immunologytumor progression
中文摘要
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英文摘要
Project Summary/Abstract
Thalidomide (Thal) and its derivatives, Lenalidomide (Len) and Pomalidomide (POM), are immune
modulatory drugs (IMiDs) used in the treatment of multiple myeloma (MM) and few other
hematological malignancies. Although they represent the backbone treatment for both newly
diagnosed and relapse/refractory MM patients, their clinical use remains mostly empirical because of
lack of suitable in vivo model systems to study their complex mechanisms of action. Murine cells are
intrinsically resistant to IMiDs because of different amino acid sequence in the IMiD binding domain of
cereblon (CRBN). By building upon our extensively validated Vk*MYC transgenic mouse model of
MM, we have generated a novel transgenic mouse, Vk*MYChCRBN, expressing the full human CRBN
(hCRBN) gene under the control of its endogenous regulatory elements, rendering it IMiD sensitive.
As previously done for the Vk*MYC model, we will extensively characterize the new Vk*MYChCRBN
model and will use it to understand the IMiD effects on the tumor and the immune system with the
ultimate goal to inform clinical practice.
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Credentialing a Genetically Engineered Clinically-Relevant Mouse Model of Multiple Myeloma
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批准号:10527365
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项目类别:
-
资助金额:$37.21万
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财政年份:2018
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负责人:Marta Chesi
-
依托单位:
Credentialing a Genetically Engineered Clinically-Relevant Mouse Model of Multiple Myeloma
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批准号:10310482
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项目类别:
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资助金额:$37.21万
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财政年份:2018
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负责人:Marta Chesi
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依托单位:
Project 3: Early detection and prevention of MM progression
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批准号:10706331
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项目类别:
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资助金额:$39.2万
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财政年份:2015
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负责人:Marta Chesi
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依托单位:
PQD2 Rational Combination of Standard Agents and Immunotherapy to Treat Myeloma
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批准号:8791848
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项目类别:
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资助金额:$34.45万
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财政年份:2014
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负责人:Marta Chesi
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依托单位:
PQD2 Rational Combination of Standard Agents and Immunotherapy to Treat Myeloma
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批准号:9335305
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项目类别:
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资助金额:$34.45万
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财政年份:2014
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负责人:Marta Chesi
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依托单位:
Immunomodulatory Therapy of Multiple Myeloma with SMAC Mimetics
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批准号:9152284
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项目类别:
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资助金额:$26.33万
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财政年份:--
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负责人:Marta Chesi
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依托单位:
Immunomodulatory Therapy of Multiple Myeloma with SMAC Mimetics
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批准号:9331584
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项目类别:
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资助金额:$28.14万
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财政年份:--
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负责人:Marta Chesi
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依托单位:
海外基金