Immuno-Oncology

免疫肿瘤学

基本信息

批准号：
10333164
负责人：
Jose R Conejo-Garcia
金额：
$ 16.22万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-02-18 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10333164
关键词：
Achievement Adoptive Cell Transfers Affect Area B-Cell Lymphomas BCL2 gene Back Beds Biological Biometry Bone Marrow Transplantation CAR T cell therapy Cancer Center Support Grant Cancer Patient Catchment Area Cell Therapy Cells Cellular Metabolic Process Cellular immunotherapy Clinical Clinical Management Clinical Services Clinical Trials Collaborations Cutaneous Melanoma Development Disease Effectiveness Epigenetic Process Funding Goals Grant Guidelines Human Immune Immune checkpoint inhibitor Immunity Immunologics Immunologist Immunooncology Immunotherapeutic agent Immunotherapy Intervention Intervention Trial Journals Laboratory Study Malignant - descriptor Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of lung Malignant neoplasm of ovary Manuscripts Metabolic Minority Groups Molecular Natural Immunity Nature Oncology Outcome Pathway interactions Patients Peer Review Play Publications Publishing Refractory Reporting Research Activity Research Personnel Resistance Role Safety Science Solid T-Lymphocyte Testing Therapy trial Toxic effect Translational Research Treatment-related toxicity Tumor Immunity Tumor-Infiltrating Lymphocytes Underrepresented Minority adaptive immunity anti-cancer base cancer cell cancer immunotherapy chimeric antigen receptor T cells design endoplasmic reticulum stress graft vs host disease immune checkpoint immunotherapy trials improved innovation insight intervention refinement melanoma member novel oncology program personalized immunotherapy preclinical study programs response success synergism therapeutic effectiveness translational medicine treatment response tumor working group

项目摘要

PROJECT SUMMARY IMMUNO-ONCOLOGY PROGRAM The overarching goal of the Immuno-Oncology Program (IO) is to develop, mechanistically understand and deliver effective and safe immunotherapies for cancer patients, with a focus on cancers that disproportionately affect patients in our catchment area. Key to success of the IO Program is the integration and synergy of basic and translational immunologists with clinicians implementing clinical trials through an interdisciplinary, “bench- to-bed-and-back” continuum. Moffitt has become a leader in state-of-the-art immunotherapy trials and to build upon this success, the research activities of IO are organized into three Specific Aims: Aim 1: To understand molecular and cellular mechanisms that exploit innate and adaptive immunity against cancer. Specific areas of focus include: 1) dissecting novel immune checkpoint inhibitory pathways and their crosstalk with other immunosuppressive mechanisms; 2) understanding coordinated cellular and humoral responses against cancer; and 3) defining metabolic alterations in innate and adaptive immune cells. Aim 2: To elucidate and target pathways governing effectiveness, resistance, and toxicity in anti- cancer immunotherapy. Specific areas of focus are: 1) providing biological and clinical insights into how to augment responses to immune checkpoint inhibitors; 2) identifying actionable epigenetic mechanisms that govern malignant progression and the effectiveness of immunotherapies; and 3) improving the effectiveness of bone marrow transplant while reducing graft versus host disease. Aim 3: To develop and implement anti-cancer cellular therapies. Specific areas of focus include targeting high priority cancers in our catchment area (e.g., melanoma, lung, cervical and ovarian cancer) by: 1) developing, implementing and refining CAR T cell therapies against human cancers, including solid malignancies; and 2) effectively treating cancer through ex vivo expanded tumor-infiltrating lymphocytes (TILs). IO has made huge impact in immuno-oncology, where IO Members have: 1) led efforts resulting in FDA approval of CAR T cells for treatment of refractory B cell lymphoma; 2) pioneered the use of TILs to achieve therapeutic responses in melanoma, and in chemo- and immunotherapy-resistant lung cancer; 3) discovered a novel targetable checkpoint inhibitory pathway in human cancer; and 4) driven changes in clinical management of CAR T and checkpoint inhibitor patients. Publications during this cycle include 136 manuscripts in journals with IF ³ 10, including NEJM, Science, Nature, Lancet Oncology, Cancer Cell and Immunity, among others. IO is comprised of 36 Members from 9 academic departments. During the reporting period, 648 cancer-related articles were published, with 21% intra-programmatic and 46% inter-programmatic collaboration rates. Current grant funding for IO is $19.3 million, of which $6.8 million is peer-reviewed, including 37% from NCI (a 36.6% increase compared to the previous cycle). Finally, IO has accrued 2,217 patients onto interventional clinical trials over the last five years.

项目概要免疫肿瘤学项目免疫肿瘤学计划 (IO) 的总体目标是开发、机械地理解和为癌症患者提供有效且安全的免疫疗法，重点关注不成比例的癌症 IO 计划成功的关键是基本要素的整合和协同。和转化免疫学家及其信徒通过跨学科的“基准测试”实施临床试验莫菲特已成为最先进的免疫治疗试验和建立的领导者。取得这一成功后，IO 的研究活动分为三个具体目标：目标 1：了解利用先天性和适应性免疫的分子和细胞机制抗癌的具体重点领域包括：1）剖析新的免疫检查点抑制途径。以及它们与其他免疫抑制机制的相互作用；2）了解协调的细胞和针对癌症的体液反应；3) 定义先天性和适应性免疫细胞的代谢改变。目标 2：阐明并确定控制抗病毒药物的有效性、耐药性和毒性的途径癌症免疫疗法的具体重点领域是：1）提供有关如何进行的生物学和临床见解。增强对免疫检查点抑制剂的反应；2）确定可操作的表观遗传机制控制恶性进展和免疫疗法的有效性；3）提高免疫疗法的有效性；骨髓移植，同时减少移植物抗宿主病。目标 3：开发和实施抗癌细胞疗法的具体重点领域包括靶向治疗。我们学区的高优先级癌症（例如黑色素瘤、肺癌、宫颈癌和卵巢癌）：1) 开发、实施和完善针对人类癌症的 CAR T 细胞疗法，包括实体瘤恶性肿瘤；2）通过离体扩增肿瘤浸润淋巴细胞（TIL）有效治疗癌症。 IO 在免疫肿瘤学领域产生了巨大影响，IO 成员：1) 领导了 FDA 的努力批准CAR T细胞治疗难治性B细胞淋巴瘤；2）率先使用TIL来实现黑色素瘤以及化疗和免疫治疗耐药的肺癌的治疗反应；3) 发现了人类癌症的新型靶向检查点抑制途径；4) 推动临床管理的变化该周期内发表的 CAR T 和检查点抑制剂患者论文包括 136 篇期刊手稿。 IF ³ 10，包括 NEJM、Science、Nature、Lancet Oncology、Cancer Cell 和 Immunity 等。由来自 9 个学术部门的 36 名成员组成。报告期内，有 648 名癌症相关人员。已发表文章，项目内合作率为 21%，项目间合作率为 46%。 IO 的赠款资金为 1930 万美元，其中 680 万美元经过同行评审，其中 37% 来自 NCI（36.6% 与上一周期相比有所增加）最终，IO 已累计有 2,217 名患者进入介入临床。过去五年的试验。