04 Immunology

04 免疫学

• 批准号: 10655531
• 负责人: JAMES P ALLISON
• 金额: $ 1.87万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-28 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10655531
• 关键词: Authorization documentation; Automobile Driving; Basic Science; Biological; Cancer Center; Cancer Center Support Grant; Cancer Vaccine Related Development; Cancer Vaccines; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Combined Modality Therapy; Data; Development; Disease; Enrollment; Environment; Failure; Fostering; Funding; Goals; Grant; Human Papilloma Virus Vaccination; Immune response; Immune system; Immunity; Immunologic Monitoring; Immunologist; Immunology; Immunotherapy; Innate Immune Response; International; Journals; Link; Mainstreaming; Malignant Neoplasms; Molecular; Nature; Paper; Patient Monitoring; Patient-Focused Outcomes; Patients; Peer Review; Population; Pre-Clinical Model; Prevention; Publishing; Relapse; Research; Resource Sharing; Sampling; Science; Side; Source; T cell therapy; T-Lymphocyte; Testing; Translating; Translational Research; Translations; Work; adaptive immune response; anti-CTLA4; anti-PD1 therapy; authority; cancer immunotherapy; cancer therapy; clinical translation; collaborative environment; combinatorial; design; experience; fecal transplantation; gut microbiome; immune checkpoint; immune checkpoint blockade; immunoregulation; improved; leukemic stem cell; member; novel; novel drug combination; novel vaccines; patient subsets; preclinical study; programs; rational design; research study; response; standard of care; stem cells; success; synergism; translational immunology; treatment response; tumor immunology; tumor microenvironment; tumor-immune system interactions; vaccination strategy; virus related cancer

PROJECT SUMMARY/ABSTRACT The Immunology Program includes 30 members (26 primary, 3 associate, 1 adjunct) from 9 departments. The program is led by Dr. James Allison, an international authority on exploring fundamental mechanisms of the immune response and checkpoint control, with co-leaders Dr. Jeffrey Molldrem, providing expertise in stem cell and translational research, and Dr. Patrick Hwu, lending his extensive experience in novel vaccines and adoptive T-cell therapies. The scientific goal of the Immunology Program is to conduct important studies in basic immunology and translate the findings into effective cancer immunotherapy. The program focuses on 4 themes: 1) immune regulation, 2) immune checkpoint blockade, 3) cancer vaccines, and 4) T-cell therapies, each with a specific aim: Aim 1: To understand fundamental mechanisms involved in regulating innate and adaptive immune responses. Aim 2: To elucidate fundamental cellular and molecular mechanisms of immune checkpoints and their impact on the tumor microenvironment by using preclinical models and clinical trials to identify the basis for failure of response to therapy or relapse. Aim 3: To identify novel targets for cancer vaccine development that will enable vaccination strategies to be more widely applied to the prevention and treatment of cancer. Aim 4: To improve the success rate of T-cell-based therapies using a combinatorial approach (T-cell therapy and checkpoint control) to improve clinical responses. Work on the Immunotherapy Platform, led by program members Drs. Allison, Padmanee Sharma, and Hwu and funded by the cancer center, spans multiple aims and serves as a mechanism to foster iterative cycles of translation between basic and clinical work by providing immune monitoring of patient samples and driving new preclinical and clinical studies by generating mechanistic data to inform rational design of new drug combinations. As of May 1, 2018, 3,434 patients have been enrolled across 118 different clinical trials. Annual direct peer-reviewed funding for the Immunology Program is $6.4M, with $1.9M (30%) from NCI grants and $4.5M (70%) from other peer-reviewed sources. Since the last submission, the program has produced 464 published papers: 184 (40%) are intraprogrammatic collaborations, 250 (54%) are interprogrammatic collaborations, and 278 (60%) are external collaborations. Sixty-five percent of articles appeared in journals with IF >5, and 31% appeared in journals with IF >10, including N Engl J Med, Nature, Cell, Science, Cancer Discov, Immunity, and Proc Natl Acad Sci USA. Program members use all 14 shared resources. Notable accomplishments during the last grant period included the demonstration that anti- CTLA-4 and anti-PD-1 therapies act on distinct T-cell populations, providing an explanation for the benefit achieved by combined therapy, and discovery of a positive correlation between gut microbiome diversity and response to immune checkpoint blockade therapy that is transferred along with fecal transplants. See the Program Highlights for other noteworthy accomplishments.

项目总结/摘要 免疫学计划包括来自9个部门的30名成员（26名主要成员，3名助理，1名助理）。的 该计划由詹姆斯·艾利森博士领导，他是一位国际权威，致力于探索 免疫反应和检查点控制，共同领导人杰弗里Molldrem博士，提供干细胞专业知识 和转化研究，以及帕特里克胡博士，凭借他在新型疫苗和 过继性T细胞疗法免疫学计划的科学目标是在基础研究中进行重要的研究。 免疫学并将发现转化为有效的癌症免疫疗法。该计划侧重于四个主题： 1)免疫调节，2）免疫检查点阻断，3）癌症疫苗，和4）T细胞疗法，每种都具有 具体目标：目标1：了解参与调节先天性和适应性免疫的基本机制 应答目的2：阐明免疫检查点的基本细胞和分子机制， 通过使用临床前模型和临床试验来确定其对肿瘤微环境的影响， 治疗无效或复发。目的3：确定癌症疫苗开发的新靶点， 将使疫苗接种策略更广泛地应用于癌症的预防和治疗。目标4： 为了提高基于T细胞的治疗的成功率，使用组合方法（T细胞治疗和 检查点控制）以改善临床反应。免疫治疗平台的工作，由项目领导 成员博士艾利森，Padmanee夏尔马，和Hwu和资助的癌症中心，跨越多个目标， 作为一种机制，通过提供 免疫监测患者样本，并通过产生机制驱动新的临床前和临床研究 数据为新药组合的合理设计提供信息。截至2018年5月1日，已入组3,434例患者 在118个不同的临床试验中。免疫学项目每年直接的同行评审资金为640万美元， 其中190万美元（30%）来自NCI赠款，450万美元（70%）来自其他同行评审来源。自上次 提交，该计划已产生464发表论文：184（40%）是内部合作， 250项（54%）是跨计划合作，278项（60%）是外部合作。百分之六十五 的文章出现在IF >5的期刊上，31%的文章出现在IF >10的期刊上，包括N Engl J Med， Nature，Cell，Science，Cancer Discov，Immunity，and Proc Natl Acad Sci USA.计划成员使用所有14个 共享资源。在上一个赠款期间取得的显著成就包括证明反- CTLA-4和抗PD-1疗法作用于不同的T细胞群，为益处提供了解释。 通过联合治疗实现，并发现肠道微生物组多样性与 对免疫检查点阻断治疗的反应，其与粪便移植一起沿着转移。看到 其他值得注意的成就的计划亮点。