DR5 Antibody Therapy for Breast Cancer
乳腺癌 DR5 抗体治疗
基本信息
- 批准号:7290715
- 负责人:
- 金额:$ 32.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-01 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdjuvantAdverse effectsAftercareAntibodiesAntibody TherapyApoptosisAppendixApplications GrantsBiological MarkersBoxingBreastBreast Cancer CellBreast Cancer TreatmentCancer CenterCancer cell lineCaspaseCell DeathCell LineCell surfaceCellsCessation of lifeClinicalClinical ResearchClinical TrialsCollaborationsCombination ChemotherapyCombined Modality TherapyComplexDeath DomainDevelopmentDisseminated Malignant NeoplasmDoseDrug Administration ScheduleDrug Delivery SystemsDrug KineticsDrug usageEngineeringEvaluationExhibitsFundingFutureGoalsGuanosine MonophosphateHepatocyteHeterogeneityHumanImplantIn VitroInduction of ApoptosisInvestigationK-Series Research Career ProgramsLicensingMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of ovaryMediatingMentorsModelingMolecular ProfilingMolecular TargetMonoclonal AntibodiesMusNormal CellPathway interactionsPatient SelectionPatientsPharmaceutical PreparationsPhasePhase I Clinical TrialsPlayPopulationPredispositionPrimatesProductionProgram DevelopmentPropertyProtein FamilyProteinsProteomicsQuality ControlRNA HelicaseRecruitment ActivityRegulationReproduction sporesResearchResearch PersonnelResistanceRestRoleScheduleSignal TransductionTNF-related apoptosis-inducing ligandTNFRSF10A geneTNFRSF10B geneTailTechnologyTestingTherapeuticTherapeutic AgentsTissue SampleTissuesToxic effectToxicologyTranslatingTreatment EfficacyTreatment ProtocolsUnited States Food and Drug AdministrationWorkXenograft Modelassay developmentcancer cellcancer therapycareerchemotherapeutic agentchemotherapyclinical efficacyclinically relevantcytotoxicitydrug developmentgenetic regulatory proteinimprovedin vivomalignant breast neoplasmneoplastic cellnonhuman primatenovelpre-clinicalpreclinical studypreventprogramsreceptorresponsesubcutaneoustherapeutic targettranslational studytrendtumortumor growth
项目摘要
Project 2 is a new project that has developed from the Career Development Program of the UAB SPORE
in Breast Cancer. The PI initially developed a novel anti-DR5 monoclonal antibody, TRA-8, which exhibited a
strong apoptosis-inducing activity against cancer cells without hepatocyte cytotoxicity. With the support of
the Career Development funds and in collaboration with our industrial sponsor, Sankyo Co, Ltd, TRA-8 has
been explored in pre-clinical studies and has moved into development as an anti-cancer candidate. The
overall goal of this proposal for the competitive renewal is to develop an effective therapeutic strategy for
treatment of breast cancer by selectively targeting DR5 with a novel monoclonal TRA-8 in combination with
chemotherapy. The central hypothesis is that breast and other cancer cells may differentially express
increasing levels of DR5 during malignant transformation and that DR5 can be selectively targeted with an
agonistic monoclonal antibody to directly induce apoptosis of cancer cells. As TRA-8 and chemotherapy
agents may utilize different but complementary pathways to trigger apoptosis, the susceptibility of breast
cancer cells to TRA-8-mediated apoptosis can be enhanced by chemotherapy agents. Furthermore, TRA-8
may improve the efficacy of chemotherapy by preventing or reversing chemo-resistance in breast cancer
cells. There are four Specific Aims: Aim 1 is to examine the efficacy of TRA-8 (anti-DR5) with and without
chemotherapy agents in murine models of orthotopic and metastatic human breast cancer; Aim 2 is to
characterize the role of the DR5/DDX3 pathway in modulating sensitivity or resistance of breast cancer cell
lines to TRA-8 induction of apoptosis, and to characterize the DR5/DDX3 pathway in human breast cancer
tissue samples; Aim 3 is to determine in vitro and in vivo synergistic mechanisms of combination therapy
with TRA-8 and chemotherapy; Aim 4 is to initiate clinical development of CS-1008 (humanized TRA-8) in
breast cancer. The proposed basic and translational studies will support the proposed clinical studies.
Accomplishment of these studies will yield a new and potentially effective therapy for breast cancer.
The goal of this research is to evaluate a new antibody for the treatment of breast cancer. The research
will identify the mechanisms for maximizing the efficacy of the antibody in combination with chemotherapy
and the development of biomarkers for predicting the response of patients in clinical trials.
项目2是从UAB SPORE职业发展计划发展而来的新项目
在乳腺癌中。 PI最初开发了一种新型抗DR5单克隆抗体TRA-8,该抗体表现出
对癌细胞有很强的细胞凋亡诱导活性,但没有肝细胞毒性。在以下人士的支持下
职业发展基金并与我们的工业赞助商 Sankyo Co, Ltd 合作,TRA-8 已
在临床前研究中进行了探索,并已作为抗癌候选药物进入开发阶段。这
该竞争性更新提案的总体目标是制定有效的治疗策略
通过使用新型单克隆 TRA-8 选择性靶向 DR5 并结合
化疗。中心假设是乳腺癌和其他癌细胞可能差异表达
恶性转化过程中 DR5 水平增加,并且 DR5 可以选择性地靶向
激动性单克隆抗体可直接诱导癌细胞凋亡。作为 TRA-8 和化疗
药物可能利用不同但互补的途径来触发细胞凋亡、乳腺癌的易感性
化疗药物可以增强TRA-8介导的癌细胞凋亡。此外,TRA-8
可以通过预防或逆转乳腺癌的化疗耐药性来提高化疗的疗效
细胞。有四个具体目标: 目标 1 是检查 TRA-8(抗 DR5)在使用和不使用的情况下的功效
原位和转移性人类乳腺癌小鼠模型中的化疗药物;目标 2 是
表征 DR5/DDX3 通路在调节乳腺癌细胞敏感性或耐药性中的作用
TRA-8 诱导细胞凋亡,并表征人类乳腺癌中的 DR5/DDX3 通路
组织样本;目标 3 是确定联合治疗的体外和体内协同机制
TRA-8 和化疗;目标 4 是启动 CS-1008(人源化 TRA-8)的临床开发
乳腺癌。拟议的基础和转化研究将支持拟议的临床研究。
这些研究的完成将产生一种新的、可能有效的乳腺癌治疗方法。
这项研究的目的是评估一种治疗乳腺癌的新抗体。研究
将确定抗体与化疗联合发挥最大功效的机制
以及开发用于预测临床试验中患者反应的生物标志物。
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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{{ truncateString('TONG ZHOU', 18)}}的其他基金
Novel Anti-HER3 Strategy for Pancreatic Cancer
治疗胰腺癌的新型抗 HER3 策略
- 批准号:
8640116 - 财政年份:2013
- 资助金额:
$ 32.6万 - 项目类别:
Novel Anti-HER3 Strategy for Pancreatic Cancer
治疗胰腺癌的新型抗 HER3 策略
- 批准号:
8512478 - 财政年份:2013
- 资助金额:
$ 32.6万 - 项目类别:
Death Receptor-mediated Apoptosis and Therapy Strategies in Ovarian Cancer
卵巢癌死亡受体介导的细胞凋亡和治疗策略
- 批准号:
7409970 - 财政年份:2007
- 资助金额:
$ 32.6万 - 项目类别:
Death Receptor-mediated Apoptosis and Therapy Strategies in Ovarian Cancer
卵巢癌死亡受体介导的细胞凋亡和治疗策略
- 批准号:
8018957 - 财政年份:2007
- 资助金额:
$ 32.6万 - 项目类别:
Death Receptor-mediated Apoptosis and Therapy Strategies in Ovarian Cancer
卵巢癌死亡受体介导的细胞凋亡和治疗策略
- 批准号:
7570628 - 财政年份:2007
- 资助金额:
$ 32.6万 - 项目类别:
Death Receptor-mediated Apoptosis and Therapy Strategies in Ovarian Cancer
卵巢癌死亡受体介导的细胞凋亡和治疗策略
- 批准号:
7771690 - 财政年份:2007
- 资助金额:
$ 32.6万 - 项目类别:
Death Receptor-mediated Apoptosis and Therapy Strategies in Ovarian Cancer
卵巢癌死亡受体介导的细胞凋亡和治疗策略
- 批准号:
7264774 - 财政年份:2007
- 资助金额:
$ 32.6万 - 项目类别:
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