将 NK 和 DC 整合到癌症治疗中-猫眼课题宝

将 NK 和 DC 整合到癌症治疗中

批准号：

7499879

负责人：

MICHAEL T LOTZE

金额：

$10.74万

依托单位：

UNIVERSITY OF PITTSBURGH AT PITTSBURGH

依托单位国家：

美国

项目类别：

财政年份：

2005

资助国家：

美国

项目状态：

已结题

起止时间：

2005-07-06 至 2010-06-30

来源：

https://reporter.nih.gov/project-details/7499879

关键词：

Acute Adam11 gene Adjuvant Adjuvant Therapy Adoptive Transfer Affinity American Society of Clinical Oncology Andro-Diane Animal Model Antigens Apoptosis Apoptotic Appearance Arsenic Attention Automobile Driving Bacteria Benign Prostatic Hypertrophy Bioinformatics Biological Biological Assay Biological Markers Biological Response Modifier Therapy Biology Biosensor Biostatistics Core Biotechnology Blood Blood Tests Breast Carcinoma CCL17 gene CCL18 gene CCL2 gene CCL22 gene CCL8 gene CD80 gene Cancer Biology Cancer Control Cancer Model Cancer Patient Cancer Therapy Evaluation Program Caring Carmustine/Cyclophosphamide/Melphalan/Prednisone/Vincristine Cell Therapy Cell physiology Cells Cellular Assay Cessation of life Charge China Chronic Chronic Disease Clinic Clinical Clinical Trials Colorectal Cancer Combined Modality Therapy Complex Containment Cross Presentation Cytokine Network Pathway Cytotoxic agent Data Dendritic Cells Depth Development Diagnosis Discrimination Disease Disease regression Distant Dose Early Diagnosis Effector Cell Elements End Point Endothelial Cells Engineering Environment Esophagitis Evaluation Event Extramural Activities Failure Family Family member Fibroblasts Frequencies Genes Genomics Glioma Goals Granzyme Head and neck structure Healed Hepatitis Human Human Genome Human Papillomavirus IL8 gene Image Immune Immune response Immunity Immunologics In Situ In Vitro Individual Inflammation Inflammatory Inflammatory Response Injection of therapeutic agent Injury Ink Interferon-alpha Interleukin-1 Interleukin-10 Interleukin-12 Interleukin-13 Interleukin-16 Interleukin-17 Interleukin-2 Interleukin-4 Interleukin-6 Intralymphatic Injections Investigational Therapies Ions Laboratories Large Intestine Carcinoma Learning Left Lymphokines MHC antigen Malignant Lymph Node Neoplasm Malignant Neoplasms Malignant neoplasm of ovary Malignant neoplasm of pancreas Malignant neoplasm of prostate Mass Spectrum Analysis Measures Mediating Mediator of activation protein Memory Methods Minor Modeling Modification Molecular Monitor Mus Mutation Natural Killer Cells Nature Necrosis Neoplasm Metastasis Neoplasms Nitric Oxide Nuclear Numbers Outcome Patients Pattern Peptide/MHC Complex Peptides Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Pharmacologic Substance Phase Phenotype Physiologic pulse Play Pre-Clinical Model Primary carcinoma of the liver cells Principal Investigator Production Program Review Group Prostaglandins Proteins Proteomics Publishing Pulse taking Quality Control Randomized Recruitment Activity Rectal Cancer Recurrence Reporting Role Safety Scientist Seminal Sensitivity and Specificity Serum Serum Proteins Shared Paranoid Disorder Signal Transduction Site Smoke Societies Solutions Specificity Specimen Staging Standards of Weights and Measures Stimulus Supercomputing Suppressor-Effector T-Lymphocytes Surface System T-Lymphocyte TNF gene Techniques Technology Testing Tetradecanoylphorbol Acetate Therapeutic Time Tissues Today Toll-like receptors Toxic effect Toxin Treatment Protocols Treatment-Related Cancer Tumor Antigens Tumor Expansion Tumor Necrosis Factor Ligand Superfamily Member 6 Twin Multiple Birth United States Food and Drug Administration Universities University of Pittsburgh Cancer Institute Vaccines Virginia Virus Virus Diseases Week base biochip cancer care cancer therapy carcinogenesis chlorambucil/dactinomycin/methotrexate protocol contextual factors cost cost effective cytokine design expectation experience falls feeding healing human study improved in vivo insight interest interleukin-23 irradiation irritation kidney cell macrophage malignant breast neoplasm melanoma member neoplastic neoplastic cell neutrophil novel novel strategies outcome forecast perforin peripheral blood programs prospective response success surface enhanced laser desorption ionization theories tumor tumor growth tumor progression vaccination strategy

中文摘要

翻译

在人类肿瘤中发现的DC、NK和T细胞几乎与预后的改善有关检查的每一种肿瘤类型。事实上，他们的招募可能会在慢性病的发展过程中发生改变炎症反应。癌症发生在慢性炎症的背景下--引发急性炎症反应诱导新的T细胞能够介导持续和更有效的抗肿瘤活性是中心这一提议的前提。瘤内直接注射NK和DC在肿瘤治疗中的应用在体外与肿瘤或作为免疫原注射的肿瘤抗原共同孵育将导致肿瘤并引发有效的适应性免疫反应。关键生物标志物的识别和使用现代蛋白质组、基因组和细胞组学策略的替代品将作为一种意味着更容易在早期疾病中测试这些策略。我们假设，通过指挥NK和DC 在谣言现场，我们可以增强对既定局部疾病的消退，促进更有效对肿瘤的系统免疫力。NK和DC之间需要协调信号以启动最佳TH1 极化，随后驱动有效的适应性T细胞对癌症的反应。事实上，在经历了20年的 NKJANK/LAK采用转移术和数年接受DC治疗的1000多名患者的经验，它是很明显，NK和DC之间的合作互动将是改变建立了对癌症的免疫反应。我们将在四个项目中对此进行调查：项目一.启动对癌症的适应性免疫反应；项目II。NK细胞诱导DCL介导的抗肿瘤免疫，以及项目IL-1同系物促进黑色素瘤的急性炎症反应。发展中的这三个项目将得到三个核心的支持：a)行政、生物信息学和生物统计核心 B)成像核心，C)蛋白质组学核心。项目I将促进临床试验的进一步发展建议用于黑色素瘤和结直肠癌患者，这些患者将在项目II和直接淋巴内注射NK成熟的DC-1肿瘤抗原或裂解物的评估将是与直接瘤内注射NK和DC的策略进行比较。

英文摘要

DCs, NK and T-cells found within human tumors have been associated with an improved prognosis in almost every tumor type examined. Indeed their recruitment may be modified during development of the chronic inflammatory response. Cancer arises in the setting of chronic inflammation - inducing an acute inflammatory response to elicit new T-cells capable of mediating sustained and more effective antitumor activity is the central premise of this proposal. Integrating NK and DC into Cancer Therapy with direct injection into tumor or coincubated ex vivo with tumor or tumor antigens administered as an immunogen, will result in tumor destruction and elicit an effective adaptive immune response. The identification of critical biomarkers and surrogates using modern proteomic, genomic, and cellomic strategies will be integrated into all projects as a means to test these strategies more readily in early disease. We hypothesize that by directing NK and DC to rumor sites in situ, that we can enhance regression of established local disease, promoting a more effective systemic immunity to tumor. Coordinate signaling is necessary between NK and DCs to initiate optimal TH1 polarization, subsequently driving an effective adaptive T-cell response to cancer. Indeed, after two decades of NKJANK/LAK adoptive transfer and several years of experience with over 1000 patients receiving DCs, it is becoming apparent that cooperative interactions between NK and DC will be necessary to modify the established immune response to cancer. We will investigate this in four projects: Project I. Initiating the Adaptive Immune Response to Cancer; Project II. NK cells induce DCl-mediated anti-rumor immunity, and Project IlL IL-1 Homolognes Promote the Acute Inflammatory Response to Melanoma. Development of these three projects will be supported by three cores: A) Administrative, Bioinformatics and Biostatistics Core B) Imaging Core, and C) Proteomics Core. Project I will enable further development of the clinical trials proposed in patients with melanoma and colorectal cancer who will be evaluated and treated in Projects II and III. Evaluation of direct intralymphatic injection of NK matured DC 1 fed tumor antigen or lysates will be contrasted with strategies using direct intratumoral injection of NK and DC.

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