Research Programs-Immunology and Immunotherapy

研究项目-免疫学和免疫治疗

• 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
• 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

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 已有的计划，基础科学免疫学计划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本知识的理解中的根本性进步转化为 癌症免疫学的治疗进展，通过密切协调和整合实验室和临床 件.然而，这种协调是高度双向的。在实验室中获得的见解， 新疗法的发展和临床发现被用来指导新的实验室研究。的 l&l计划是建立在基础免疫学非常强大的基础上，其成员 包括一个杰出的研究小组，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计划还产生了一个 各种新的免疫学方法，包括促进免疫学策略的谱 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）使同种异体干细胞中的移植物抗宿主病最小化的方法 移植; 3）移植物抗肿瘤反应的优化; 4）用于递送 肿瘤抗原疫苗; 5）通过阻断CTLA-4增强抗肿瘤免疫应答。L&L 该计划有46个独立但高度互动的成员，代表实验室和临床 11个部门的调查人员。该计划是由伊拉梅尔曼（主席，细胞生物学; YCC助理 科学主任），桥梁的基础和临床l&l组件。梅尔曼博士是一位 DC的抗原呈递机制，最近集中于应用基础免疫学 人类癌症免疫疗法的发展原则。三位副领导密切合作 和梅尔曼博士一起，直接参与了这个项目Warren Shlomchik博士负责监督基础癌症 免疫学组成部分，而迈克尔吉拉迪博士和弗朗辛福斯博士负责 免疫治疗成分。每月举行一次会议， 致力于癌症免疫学的成员，负责实施免疫疗法的工作组 议定书，一般务虚会，系列研讨会和新设立的种子赠款竞争，以资助创新 免疫疗法的方法。经同行审查的支助的直接费用总额为2 080万美元（费用总额为3 010万美元）。 直接费用供资总额为2 840万美元（费用总额为3 920万美元）。在上一个补助期，613个癌症相关的 发表的论文中，23%是方案内的，11%是方案间的。