A Mouse Model to Assess Long Term Immunotherapy-related Adverse Effects in Children
评估儿童长期免疫治疗相关不良反应的小鼠模型
基本信息
- 批准号:10474298
- 负责人:
- 金额:$ 40.46万
- 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:2018-09-07 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAdverse effectsAdverse eventAffectAgeAntibodiesAntigen-Presenting CellsAttentionAutoimmuneB-Cell LeukemiaBinding ProteinsCTLA4 geneCancer ModelCancer PatientCardiovascular systemCell TherapyCell physiologyChemotherapy and/or radiationChildChildhoodChildhood LeukemiaClinical TrialsConduct Clinical TrialsCytolysisDataDefectDevelopmentDiseaseEndocrine systemHematologic NeoplasmsHumanImmune checkpoint inhibitorImmune responseImmunotherapeutic agentImmunotherapyInflammationInvestigationInvestigational TherapiesKnock-inLeadLifeLinkLong-Term EffectsMalignant Childhood NeoplasmMediatingMetastatic MelanomaModelingMolecularMusNeuroblastomaNon-Small-Cell Lung CarcinomaNormal tissue morphologyOperative Surgical ProceduresOrganPathogenesisPatientsPatternPediatric OncologyPhase II Clinical TrialsPlayPre-Clinical ModelPreventionProtocols documentationPublicationsRadiation therapyRenal functionReportingReproductionResearchRoleSerious Adverse EventSignal PathwaySolidSolid NeoplasmSystemT-LymphocyteTestingTherapeutic EffectTissuesToxic effectTranslational ResearchTranslationsTumor ImmunityWorkanti-CTLA4anti-CTLA4 antibodiesanti-PD-1anti-PD-L1antibody immunotherapyautoimmune pathogenesiscancer immunotherapycancer therapychimeric antigen receptorconventional therapycytotoxicityeffector T cellfrontiergenetic approachimmune-related adverse eventsimmunotherapy clinical trialsin vivoindustry partnerinnovationipilimumabliver functionmouse modelnovelpediatric patientsphase I trialpreventresponsescreeningsialic acid binding Ig-like lectinside effectstandard of caretargeted treatmenttissue injurytooltumor
项目摘要
Cancer immunotherapy has emerged as the most potent and durable treatment for cancers in recent
years. In some solid tumors and hematological malignancies, immunotherapy has become the standard of care,
joining the ranks of conventional treatment such as surgery, chemotherapy, radiation and targeted therapy.
Chimeric antigen receptor – T (CAR-T) therapy has made impressive progress in treatment of pediatric
leukemia. It is highly anticipated that checkpoint inhibitor antibody immunotherapy, such anti-PD-1, anti-PD-L1,
and anti-CTLA4, will be tested in pediatric cancers in clinical trials (some Phase 1 trials are ongoing) . However,
the autoimmune adverse events (irAE) associated with the immunotherapy is quite severe, with greater than
50% of patients developing grade 3 and 4 organ toxicity in adult clinical trials. The report on a Phase 1 trial of
anti-CTLA4 antibody (Ipilimumab) on pediatric cancer patients suggested similar rate of irAE as observed in
adult, although the observation period is too short to identify issues unique for developmental defects unique for
pediatric patients. Therefore, the major challenges in research effort for pediatric cancer immunotherapy are (1)
establishing mouse models to recapitulate irAE, especially the long term irAE unique for pediatric patients; (2)
using mouse models to study the irAE pathogenesis (3) searching new targets to reduce irAE without impeding
anti-tumor efficacy.
Damage related molecular patterns (DAMPs) play an important role in regulating tissue damages,
antigen presenting cells activation and effector T cell functions. Our previous work demonstrated that CD24-
Siglec signaling pathway suppresses inflammation triggered by DAMPs. We have established a mouse model
that faithfully recapitulates the irAEs in major organs that have been reported in anti-CTLA 4 and anti-
PD-1 immunotherapy clinical trials. Here we propose to characterize the long term irAE in mouse model, and
to examine the role of DAMPs-binding protein CD24 and Siglecs in irAE pathogenesis.
近年来,癌症免疫疗法已成为最有效、最持久的癌症治疗方法
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Targeting HIF-1α abrogates PD-L1-mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues.
- DOI:10.1172/jci150846
- 发表时间:2022-05-02
- 期刊:
- 影响因子:15.9
- 作者:Bailey, Christopher M.;Liu, Yan;Liu, Mingyue;Du, Xuexiang;Devenport, Martin;Zheng, Pan;Liu, Yang;Wang, Yin
- 通讯作者:Wang, Yin
CD24-Fc suppression of immune related adverse events in a therapeutic cancer vaccine model of murine neuroblastoma.
- DOI:10.3389/fimmu.2023.1176370
- 发表时间:2023
- 期刊:
- 影响因子:7.3
- 作者:
- 通讯作者:
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Yin Wang其他文献
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{{ truncateString('Yin Wang', 18)}}的其他基金
A Mouse Model to Assess Long Term Immunotherapy-related Adverse Effects in Children
评估儿童长期免疫治疗相关不良反应的小鼠模型
- 批准号:
10231128 - 财政年份:2018
- 资助金额:
$ 40.46万 - 项目类别:
Molecular Programs for Stem Cells of Hematological Malignancies
血液恶性肿瘤干细胞的分子计划
- 批准号:
8302757 - 财政年份:2012
- 资助金额:
$ 40.46万 - 项目类别:
Molecular Programs for Stem Cells of Hematological Malignancies
血液恶性肿瘤干细胞的分子计划
- 批准号:
8449111 - 财政年份:2012
- 资助金额:
$ 40.46万 - 项目类别:
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