Immunology of human malignant melanoma initiating cells
人类恶性黑色素瘤起始细胞的免疫学
基本信息
- 批准号:8532856
- 负责人:
- 金额:$ 37.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2017-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAffinityApplications GrantsBRAF geneBiological MarkersBiological ProductsBiopsy SpecimenBlood CirculationCellsCerealsClinicalCombined Modality TherapyDevelopmentDiseaseDissectionDisseminated Malignant NeoplasmDrug FormulationsEarly DiagnosisEvolutionExcisionGoalsHematopoieticHumanImmuneImmune TargetingImmunityImmunocompromised HostImmunologyImmunotherapeutic agentImmunotherapyIn VitroIndiumLaboratoriesLigandsMS4A1 geneMalignant NeoplasmsMediatingMediator of activation proteinMelanoma CellMetastatic MelanomaMinorityModalityModelingMonoclonal AntibodiesMulti-Drug ResistanceMusMutateNatureNeoplasm MetastasisOperative Surgical ProceduresOrganOutcomePathway interactionsPatientsPeripheralPeripheral Blood Mononuclear CellPopulationRegional Lymph Node InvolvementResearchResistanceRiceSkin NeoplasmsStem cellsSurvival RateTherapeuticTreatment ProtocolsTumor ImmunityTumor TissueVirulenceVirulentVisceralXenograft ModelXenograft procedureantibody-dependent cell cytotoxicitycancer stem cellclinical applicationconventional therapyeffective therapyin vivomelanomanovelnovel strategiesnovel therapeuticsoutcome forecastpre-clinicalreceptorresearch clinical testingresearch studyresponseself-renewaltherapy resistanttumortumor growthtumor progression
项目摘要
DESCRIPTION (provided by applicant): Malignant melanoma initiating cells (MMICs) are minority subpopulations in which clinical virulence resides as a consequence of unlimited self-renewal capacity, resulting in inexorable tumor progression and potential metastasis. Our laboratories have recently identified human MMICs and shown them to express the targetable biomarker and multidrug resistance transporter, ABCB5 (Nature, Jan 17, 2008). In this study, proof of principle of immune-mediated MMIC destruction and consequent inhibition of tumor growth was demonstrated. More recently, we have shown that MMICs employ mechanisms to thwart endogenous anti-tumor immunity via the B7-2 and PD1 pathways (Cancer Res, Jan 15, 2010). This proposal seeks to further advance these findings in a translationally-relevant manner with the goal of accelerating progress toward clinical application of anti- melanoma immune therapies specifically targeting MMICs. The specific aims of this proposal are: (1) Characterization of ABCB5+ MMIC response to immunotherapy in human patients and assessment/prediction of MMIC therapeutic response; (2) In vivo dissection of antitumor immunity pathway interactions with MMIC in a novel humanized xenotransplantation model, melanoma to hu-PBMC NOD-scid IL2r3null mice; and (3) Preclinical immunomodulatory/MMIC-targeted combination therapies. This initiative should enhance the rapid development and refinement of targeted immunotherapies directed against MMICs, and thus holds great promise for rapid evolution to clinical testing.
描述(由申请方提供):恶性黑色素瘤起始细胞(MMIC)是少数亚群,由于无限的自我更新能力,其存在临床毒力,导致不可阻挡的肿瘤进展和潜在转移。我们的实验室最近鉴定了人MMIC,并显示它们表达靶向生物标志物和多药耐药转运蛋白ABCB 5(Nature,2008年1月17日)。在这项研究中,证明了免疫介导的MMIC破坏和随后抑制肿瘤生长的原理。最近,我们已经表明MMIC采用通过B7-2和PD 1途径阻碍内源性抗肿瘤免疫的机制(Cancer Res,2010年1月15日)。该提案旨在以预防相关的方式进一步推进这些发现,目的是加速特异性靶向MMIC的抗黑色素瘤免疫疗法的临床应用进展。本提案的具体目的是:(1)表征ABCB 5 + MMIC对人类患者免疫治疗的反应,并评估/预测MMIC治疗反应;(2)在新型人源化异种移植模型(hu-PBMC NOD-scid IL 2 r3 null小鼠的黑色素瘤)中体内解剖抗肿瘤免疫途径与MMIC的相互作用;以及(3)临床前免疫调节/MMIC靶向联合治疗。这一举措将促进针对MMIC的靶向免疫疗法的快速开发和完善,从而为快速发展到临床测试带来巨大希望。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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Markus H. Frank其他文献
Méthodes diagnostiques et thérapeutiques se rapportant à des cellules souches cancéreuses
癌症细胞的诊断和治疗方法
- DOI:
- 发表时间:
2009 - 期刊:
- 影响因子:0
- 作者:
Markus H. Frank;Natasha Y. Frank - 通讯作者:
Natasha Y. Frank
Utilisation de polynucléotides de la subtilisine (RNR9) pour obtenir une résistance à un pathogène dans les plantes
利用枯草杆菌多核苷酸 (RNR9) 获得植物病原体的抗性
- DOI:
- 发表时间:
2008 - 期刊:
- 影响因子:0
- 作者:
Markus H. Frank;P. Schweizer;Dimitar Douchkov - 通讯作者:
Dimitar Douchkov
Caveolin 1 and 2 enhance the proliferative capacity of BCAM-positive corneal progenitors
- DOI:
10.1038/s41598-024-81283-4 - 发表时间:
2025-02-24 - 期刊:
- 影响因子:3.900
- 作者:
Yuzuru Sasamoto;Shoko Kiritoshi;Catherine A. A. Lee;Yoshiko Fukuda;Gabrielle Martin;Bruce R. Ksander;Markus H. Frank;Natasha Y. Frank - 通讯作者:
Natasha Y. Frank
Procédé d'augmentation de la résistance aux champignons dans les plantes
植物中香菇抵抗力的增强过程
- DOI:
- 发表时间:
2007 - 期刊:
- 影响因子:0
- 作者:
Holger Schultheiss;Markus H. Frank;Caroline Höfle - 通讯作者:
Caroline Höfle
Angiogenin Released from ABCB5sup+/sup Stromal Precursors Improves Healing of Diabetic Wounds by Promoting Angiogenesis
ABCB5 阳性基质前体细胞释放的血管生成素通过促进血管生成改善糖尿病伤口愈合
- DOI:
10.1016/j.jid.2021.10.026 - 发表时间:
2022-06-01 - 期刊:
- 影响因子:5.700
- 作者:
Karmveer Singh;Pallab Maity;Albert Kallon Koroma;Abhijit Basu;Rajeev Kumar Pandey;Seppe Vander Beken;Philipp Haas;Linda Krug;Adelheid Hainzl;Anca Sindrilaru;Christiane Pfeiffer;Meinhard Wlaschek;Natasha Y. Frank;Markus H. Frank;Christoph Ganss;András Bánvölgyi;Norbert Wikonkál;Sabine Eming;Irena Pastar;Marjana Tomic-Canic;Karin Scharffetter-Kochanek - 通讯作者:
Karin Scharffetter-Kochanek
Markus H. Frank的其他文献
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{{ truncateString('Markus H. Frank', 18)}}的其他基金
Multicomponent Therapy for Age-related Skin Stem Cell Deficiency
治疗与年龄相关的皮肤干细胞缺乏症的多成分疗法
- 批准号:
10707346 - 财政年份:2022
- 资助金额:
$ 37.71万 - 项目类别:
Multicomponent Therapy for Age-related Skin Stem Cell Deficiency
治疗与年龄相关的皮肤干细胞缺乏症的多成分疗法
- 批准号:
10494654 - 财政年份:2022
- 资助金额:
$ 37.71万 - 项目类别:
Stem Cell Integral Membrane Transporter ABCB5 and Dermal Regeneration
干细胞整体膜转运蛋白 ABCB5 和真皮再生
- 批准号:
10494660 - 财政年份:2022
- 资助金额:
$ 37.71万 - 项目类别:
Stem Cell Integral Membrane Transporter ABCB5 and Dermal Regeneration
干细胞整体膜转运蛋白 ABCB5 和真皮再生
- 批准号:
10707397 - 财政年份:2022
- 资助金额:
$ 37.71万 - 项目类别:
Immunology of human malignant melanoma initiating cells
人类恶性黑色素瘤起始细胞的免疫学
- 批准号:
8239174 - 财政年份:2012
- 资助金额:
$ 37.71万 - 项目类别:
Immunology of human malignant melanoma initiating cells
人类恶性黑色素瘤起始细胞的免疫学
- 批准号:
8685190 - 财政年份:2012
- 资助金额:
$ 37.71万 - 项目类别:
Immunology of human malignant melanoma initiating cells
人类恶性黑色素瘤起始细胞的免疫学
- 批准号:
9112874 - 财政年份:2012
- 资助金额:
$ 37.71万 - 项目类别:
Melanoma Stem Cells, Vasculogenesis and Neoplastic Progression
黑色素瘤干细胞、血管生成和肿瘤进展
- 批准号:
8307737 - 财政年份:2008
- 资助金额:
$ 37.71万 - 项目类别:
Melanoma Stem Cells, Vasculogenesis and Neoplastic Progression
黑色素瘤干细胞、血管生成和肿瘤进展
- 批准号:
8109826 - 财政年份:2008
- 资助金额:
$ 37.71万 - 项目类别:
Melanoma Stem Cells, Vasculogenesis and Neoplastic Progression
黑色素瘤干细胞、血管生成和肿瘤进展
- 批准号:
7692241 - 财政年份:2008
- 资助金额:
$ 37.71万 - 项目类别:
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