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.

免疫学和免疫治疗 (l&l) 计划代表了两个核心组成部分的合并现有项目、基础科学免疫学项目和免疫治疗导向的淋巴瘤程序。 L&L 计划的总体使命是将我们对基础知识的理解转化为根本性进步。通过密切协调和整合实验室和临床，癌症免疫学与治疗进展相结合成分。然而，这种协调是高度双向的。在实验室获得的见解用于提供信息新疗法的开发和临床发现被用来指导新的实验室研究。这 l&l 计划建立在基础免疫学方面异常坚实的基础之上，其成员由一群杰出的研究人员组成，负责 T 细胞和 B 细胞发育的重大进展，树突状细胞功能、Toll 样受体和抗原呈递。此外，l&l 计划还制定了多种新型免疫治疗方法，包括一系列免疫策略通过该计划的实验室进展，包括 1) 通过体外诱导抗肿瘤免疫光免疫疗法（ECP）； 2) 减少同种异体干细胞移植物抗宿主病的方法移植； 3) 移植物抗肿瘤反应的优化； 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 计划有 46 名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。该项目由 Ira Mellman（细胞生物学主席；YCC 助理）领导科学总监），连接基础和临床 L&L 组件。梅尔曼博士是这方面的专家 DC 抗原呈递机制，最近集中于应用基本免疫学人类癌症免疫疗法的发展原则。三位副领导密切合作与梅尔曼博士一起，是该计划的直接子组成部分。 Warren Shlomchik 博士负责基础癌症治疗免疫学部分，而 Michael Girardi 博士和 Francine Foss 博士负责免疫治疗成分。沟通和计划重点通过每月一次的会议来维持致力于癌症免疫学的成员，一个负责实施免疫疗法的工作组协议、一般务虚会、研讨会系列以及新设立的种子资助竞赛，以资助创新免疫疗法的方法。同行评审支持的直接成本总额为 20.8 美元（总成本为 3010 万美元）。直接费用总额为 2,840 万美元（总费用为 3,920 万美元）。在上一个资助期内，有 613 名癌症相关患者已发表论文，其中 23% 为程序内论文，11% 为程序间论文。