Research Programs-Immunology and Immunotherapy

研究项目-免疫学和免疫治疗

基本信息

批准号：
7513241
负责人：
IRA S MELLMAN
金额：
$ 2.14万
依托单位：
YALE UNIVERSITY
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：
2007-08-09 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7513241
关键词：
Acute Address Adjuvant Agonist Allogenic Allografting Animal Model Antibodies Antigen Presentation Antigen Receptors Antigens Apoptosis Apoptotic Area Ascaridil Autoimmune Process Automobile Driving Award B-Cell Development B-Lymphocytes Basic Science Blood Cells Bone Marrow Transplantation CD8B1 gene Cancer Immunology Science Cell physiology Cells Cellular biology Characteristics Charge Chronic-Phase Myeloid Leukemia Clinic Clinical Clinical Investigator Clinical Trials Coculture Techniques Collaborations Combined Modality Therapy Communication Cross Presentation Cutaneous Cutaneous Lymphoma Cytotoxic T-Lymphocytes Dendritic Cells Depth Development Developmental Therapeutics Program Direct Costs Disease Dominant Negative Receptor Dominant-Negative Mutation Dose-Limiting Enrollment Ensure Family Fellowship Foundations Funding Goals Graft Rejection Graft-Versus-Tumor Induction Grant Head and Neck Squamous Cell Carcinoma Hematologic Neoplasms Human Human Development Human Papillomavirus Immune Immune response Immune system Immunity Immunologics Immunology Immunosuppression Immunotherapeutic agent Immunotherapy In Vitro In complete remission Incidence Infusion procedures Ingestion Interleukin-10 Joints Laboratories Laboratory Study Lead Leadership Lesion Link Lymphocyte Lymphoma Malignant Neoplasms Memory Methodology Methods Microscopic Minor Histocompatibility Antigens Mission Modeling Modification Molecular Monoclonal Antibodies Mus Natural Immunity Nature Necrosis Non-Small-Cell Lung Carcinoma Organ Transplantation Paper Pathway interactions Patients Peer Review Peptides Phase I Clinical Trials Phenotype Pilot Projects Population Procedures Process Production Properdin Protocols documentation Publishing Radiation therapy Radiobiology Rapid Access to Intervention Development Rate Reagent Reproduction spores Research Research Personnel Risk Safety Science Scientific Advances and Accomplishments Seeds Series Signal Transduction Solid Neoplasm Source Standards of Weights and Measures Stem cell transplant Sum System T cell regulation T memory cell T-Lymphocyte TNFRSF5 gene Techniques Testing Therapeutic Therapeutic immunosuppression Therapy Clinical Trials Titrations Tobacco Toll-like receptors Toxic effect Transforming Growth Factors Translating Translational Research Translations Transplantation Treatment Protocols Tumor Antigens Tumor Cell Derivative Vaccine Tumor Immunity Tumor-Infiltrating Lymphocytes Universities Vaccination Work anergy antigen processing base cancer cell cancer immunology function cancer immunotherapy clinically relevant concept conditioning cost design fundamental research graft vs host disease graft vs leukemia effect human data immunogenic in vivo innovation insight leukemia/lymphoma malignant breast neoplasm melanoma member monocyte nanoparticle neoplastic cell novel particle pathogen poly(D,L-lactide-co-glycolide)polylactic acid-polyglycolic acid copolymer prevent programs receptor function reconstitution research clinical testing response stem cell therapy tumor unpublished works vaccine development vector

项目摘要

The Immunology and Immunotherapy (l&l) Program represents the merger of the central components of two pre-existing programs, the basic science Immunology Program and the immunotherapy-oriented Lymphoma Program. The l&l Program's overall mission is to translate fundamental advances in our understanding of basic cancer immunology to therapeutic advances, by closely coordinating and integrating the laboratory and clinical components. This coordination is highly bidirectional, however. Insights gained in the laboratory used to inform the development of new therapies, and discoveries in the clinic are used to direct new laboratory studies. The l&l Program is built upon an exceptionally strong foundation in fundamental immunology, its members comprising an illustrious group of investigators responsible for major advances in T- and B-cell development, dendritic cell function, Toll-like receptors, and antigen presentation. Moreover, the l&l Program has produced a variety of novel immunotherapeutic approaches, encompassing a spectrum of immunologic strategies facilitated by the Program's laboratory advances, including 1) the induction of anti-tumor immunity via extracorporeal photoimmunetherapy (ECP); 2) methods of minimizing graft-versus-host disease in allogeneic stem cell transplantation; 3) optimization of graft-versus-tumor responses; 4) biodegradable nanoparticles for delivery of tumor antigen vaccines; 5) enhancement of anti-tumor immune responses by blockade of CTLA-4. The l&l Program has 46 independent but highly interactive members representing both laboratory and clinical investigators from 11 departments. The program is led by Ira Mellman (Chair, Cell Biology; YCC Associate Director for Science), bridges the fundamental and clinical l&l components. Dr. Mellman is an expert in the mechanisms of antigen presentation by DCs and more recently has focused on applying basic immunological principles to the development of human cancer immunotherapies. Three Associate Leaders, working closely with Dr. Mellman, direct subcomponents of the Program. Dr. Warren Shlomchik oversees the basic cancer immunology component, while Dr. Michael Girardi and Dr. Francine Foss have responsibility for the immunotherapy component. Communication and programmatic focus are maintained by a monthly meeting of members devoted to cancer immunology, a working group charged with implementing immunotherapy protocols, a general retreat, a seminar series, and a newly established seed grant competition to fund innovative approaches to immunotherapy. Total peer-reviewed support is $20.8 direct costs ($30.1 million total costs). Overall funding is $28.4 million in direct costs ($39.2 million total costs). In the last grant period, 613 cancerrelated papers were published, of which 23% were intraprogrammatic and 11% were interprogrammatic.

免疫学和免疫疗法（L＆L）计划代表了两个中心组成部分的合并现有计划，基础科学免疫学计划和面向免疫疗法的淋巴瘤程序。 L＆L计划的整体使命是翻译我们对基本的理解的基本进步通过密切协调和整合实验室和临床的癌症免疫学对治疗进展成分。但是，这种协调是高度双向的。用于告知的实验室中获得的见解新疗法的发展和诊所发现的发现用于指导新的实验室研究。这 L＆L计划建立在基本免疫学上异常强大的基础之上，其成员由一群杰出的研究人员组成，负责T-和B细胞开发的重大进展，树突状细胞功能，Toll样受体和抗原表现。此外，L＆L计划已经产生了各种新型免疫治疗方法，包括促进的一系列免疫学策略根据该计划的实验室进步，包括1）通过体外诱导抗肿瘤免疫摄影摄影（ECP）； 2）最大程度地减少同种异体干细胞中移植物抗宿主病的方法移植； 3）优化移植物与肿瘤反应； 4）可生物降解的纳米颗粒用于输送肿瘤抗原疫苗； 5）通过阻断CTLA-4增强抗肿瘤免疫反应。 L＆L 计划具有46个独立但高度互动的成员，代表实验室和临床来自11个部门的调查人员。该计划由Ira Mellman（细胞生物学主席； YCC同事）领导科学总监），桥接基本和临床L＆L组件。梅尔曼博士是 DC和最近的抗原表现机制重点是应用基本免疫学人类癌免疫疗法发展的原则。三名副领导人，紧密工作与该计划的直接子组成部分Mellman博士。 Warren Shlomchik博士监督基本癌症免疫学部分，而迈克尔·吉拉迪（Michael Girardi）博士和弗朗辛·福斯（Francine Foss）博士对免疫疗法成分。通过每月一次的会议来维持沟通和程序重点专门致力于癌症免疫学的成员，这是一个负责实施免疫疗法的工作组协议，一般务虚会，研讨会系列和新成立的种子赠款竞争，以资助创新性免疫疗法的方法。同行评审的总支持为20.8美元直接成本（总成本为3010万美元）。总体资金为2840万美元的直接成本（3920万美元的总成本）。在最后一个赠款期间，有613次取消论文发表了，其中23％是插图内的，有11％是诠释截图。