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.

免疫学和免疫疗法(L和L)项目代表着两个项目的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治疗的淋巴瘤 程序。L和L计划的总使命是将我们对基础的认识的根本进展转化为 通过密切协调和整合实验室和临床，癌症免疫学促进治疗进展 组件。然而，这种协调是高度双向的。在实验室中获得的洞察力用于向 新疗法的开发和临床上的发现被用来指导新的实验室研究。这个 L和L计划建立在非常坚实的基础免疫学基础上，其成员 由一组杰出的研究人员组成，负责T细胞和B细胞发展的重大进展， 树突状细胞功能、Toll样受体和抗原呈递。此外，L和L的节目产生了一个 多种新的免疫治疗方法，包括促进的一系列免疫策略 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)减少异基因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 肿瘤抗原疫苗；5)阻断CTLA-4增强抗肿瘤免疫反应。L与L 该计划有46名独立但高度互动的成员，分别代表实验室和临床 来自11个部门的调查人员。该项目由Ira Mellman(YCC协会成员，细胞生物学主席)领导 L和L科学总监)，为基础和临床组件架起桥梁。梅尔曼博士是一位 树突状细胞的抗原提呈机制以及最近的研究重点是应用基础免疫学 人类癌症免疫疗法发展的原则。三位协理领导，密切合作 与梅尔曼博士一起，该计划的直接子组成部分。沃伦·什洛姆奇克博士负责监督基础癌症 免疫学部分，而迈克尔·吉拉尔迪博士和弗朗辛·福斯博士负责 免疫治疗组件。沟通和方案重点由每月一次的 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，一般静修，研讨会系列，以及新设立的种子赠款竞赛，以资助创新 免疫治疗的方法。经同行评审的支助总费用为2080万美元(总费用为3010万美元)。 资金总额为2840万美元的直接费用(3920万美元的总费用)。在上次资助期内，与癌症有关的有613宗 发表了论文，其中23%是方案内论文，11%是方案间论文。