Cancer Therapeutics and Host Response Research Program

癌症治疗和宿主反应研究计划

基本信息

批准号：
10625756
负责人：
Christian Jobin
金额：
$ 7.78万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10625756
关键词：
Acceleration Address Advanced Malignant Neoplasm Affect Antineoplastic Agents Authorization documentation Award BCL2L1 gene Bacteria Basic Science Biomedical Engineering Blood Brain Cancer Biology Cancer Center Cancer Center Support Grant Cancer Patient Cell physiology Cells Clinic Clinical Clinical Investigator Clinical Research Clinical Trials Clinical Trials Design Collaborations Colorectal Combined Modality Therapy Complex Cyclic GMP Development Direct Costs Disease Drug Interactions Enrollment Epithelium Florida Foundations Funding Future Grant Health Hematopoietic stem cells Histone Deacetylase Immune Immune Evasion Immune response Immune system Immunobiology Immunology Immunooncology Immunosuppression Immunotherapeutic agent Immunotherapy Infection Inflammation Infrastructure Institution Intervention Intervention Trial Investments Laboratory Scientists Leadership Legal patent Life Lung Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of lung Mediating Medicine Mentors Messenger RNA Microbe Modality Modeling Mutagens Natural Products Non-Small-Cell Lung Carcinoma Pathway interactions Patients Peer Review Pharmaceutical Chemistry Phase I Clinical Trials Population Postdoctoral Fellow Preparation Process Production Property Publications Publishing RNA RNA vaccine Refractory Research Research Personnel Resources STAT3 gene Scientist Sea Strategic Planning Structure Therapeutic Therapeutic Research Time Training Translating Translations Tumor Immunity Underrepresented Minority United States National Institutes of Health Universities Vaccines Woman Work authority base biobank biomedical referral center cancer immunobiology cancer therapy carcinogenesis chimeric antigen receptor T cells citizen science clinical candidate clinical development clinical trial protocol college cytotoxic design drug metabolism early phase clinical trial equity, diversity, and inclusion first-in-human frontier graduate student human study individualized medicine inhibitor innovation leukemia meetings member metabolomics microbial microbiome microorganism nanoparticle neoplastic cell new combination therapies new therapeutic target novel novel therapeutics patient oriented patient population pre-clinical programs protocol development rational design recruit research clinical testing response screening small molecule targeted treatment translational immunology treatment response treatment trial trial design tumor tumor progression vaccine trial working group

项目摘要

CANCER THERAPEUTICS AND HOST RESPONSE (CTHR) PROGRAM: ABSTRACT The University of Florida Health Cancer Center (UFHCC) CTHR program integrates investigators with expertise in microbiome, immunology, cancer biology, bioengineering, medicinal chemistry, and clinical trial development to advance cancer treatment. CTHR is led by Sayour, an expert in immuno-oncology, and Jobin, an authority on microbiome and cancer. CTHR is comprised of 62 members from 19 departments in 7 colleges, including 19 members recruited since 2016. CTHR members support the scientific aims to 1) define cancer immunobiology and develop novel immunotherapies; 2) elucidate microbiome function in cancer development and therapeutics; 3) identify new targeted therapies engaging key cancer pathways; and, 4) translate discoveries to new clinical trials. Key progress from the program included i) investments in cGMP facilities enabled pan-cancer platforms for multiple novel immunotherapies; ii) initiation of a first-in-human mRNA-nanoparticle vaccine trial (NCT04573140); iii) FDA IND approval for an innovative CAR-T against CD70+ malignancies; iv) novel finding that microbiome from immunotherapeutic-responsive non-small cell lung cancer patients confers responsiveness in preclinical lung models; and, v) discovery and development of new therapeutic compounds including complex cytotoxic molecules from sea life and rationally designed PROTACs against BCL-XL, now in a phase I clinical trial. The program translates basic discoveries to the clinic through the IIT Think Tank. CTHR has a peer- reviewed funding base of >$9.1M/yr in direct costs (up 23% since 2019), representing 72 peer-reviewed projects, of which 27 are from NCI ($3.2M direct costs), including 13 MPI awards. Since 2016, CTHR members generated 1,276 cancer-relevant publications, 24% with impact factors >10, of which 38% are intra-programmatic, 32% inter-programmatic, and 67% multi-institutional. The percent of clinicians publishing collaboratively with basic or population scientists nearly doubled to 59%. CTHR members had 39 new patents awarded. Since 2016, CTHR launched 41 institutional interventional trials, including 39 treatment trials. Between 2016 and 2021, 15 research findings from UFHCC members were translated into clinical trials (13 at UF) through laboratory scientist/clinical investigator collaborations. Since 2016, CTHR clinical investigators enrolled 1,199 patients on treatment trials, and in 2021 enrolled 174 of the 299 patients on UFHCC treatment trials. To accelerate clinical research, since 2019, UFHCC recruited 8 clinical investigators to CTHR with protected time and resources to develop IITs. CTHR mentors trained 194 graduate students and 92 postdoctoral trainees, of whom 44% were women; ~10% underrepresented minorities (URM). There were 25 trainees (12 women; 5 URMs) supported by NIH training grants. CTHR leadership and members are committed to the plan to enhance diversity through recruitment in partnership with the Associate Director for Diversity, Equity, and Inclusion. Future plans, aligned with the UFHCC strategic plan, include recruitment in translational immunology, microbiome and carcinogenesis, P01 grants (e.g., brain, microbiome, lung), and targeted recruitment of clinical investigators (e.g., women's, lung, blood).

癌症治疗和宿主反应 (CTHR) 计划：摘要佛罗里达大学健康癌症中心 (UFHCC) CTHR 项目将研究人员与专业知识融为一体微生物组、免疫学、癌症生物学、生物工程、药物化学和临床试验开发推进癌症治疗。 CTHR 由免疫肿瘤学专家 Sayour 和权威 Jobin 领导关于微生物组和癌症。 CTHR由来自7个学院19个系的62名成员组成，其中19名自 2016 年起招募成员。CTHR 成员支持以下科学目标：1) 定义癌症免疫生物学并开发新型免疫疗法； 2）阐明微生物组在癌症发展和治疗中的功能； 3）确定涉及关键癌症途径的新靶向疗法； 4) 将发现转化为新的临床试验。该计划的主要进展包括 i) 对 cGMP 设施的投资支持泛癌平台用于多种新型免疫疗法； ii) 启动首次人体 mRNA 纳米颗粒疫苗试验（NCT04573140）； iii) FDA 批准针对 CD70+ 恶性肿瘤的创新 CAR-T； iv) 新颖的发现来自免疫治疗有反应的非小细胞肺癌患者的微生物组具有反应性在临床前肺模型中； v) 发现和开发新的治疗化合物，包括复合物来自海洋生物的细胞毒性分子和针对 BCL-XL 合理设计的 PROTAC，目前处于 I 期临床审判。该计划通过印度理工学院智库将基本发现转化为临床。 CTHR 有一个同行审查的直接成本每年超过 910 万美元（自 2019 年以来增长 23%），代表 72 个同行评审项目，其中 27 个来自 NCI（直接成本 320 万美元），其中包括 13 个 MPI 奖项。自 2016 年以来，CTHR 成员产生了 1,276 篇癌症相关出版物，24% 的影响因子 >10，其中 38% 为程序内出版物，32% 跨项目，67% 跨机构。与基础或临床医生合作发表论文的百分比人口科学家几乎翻了一番，达到 59%。 CTHR 成员获得了 39 项新专利。自 2016 年以来，CTHR 开展了41项机构干预试验，其中包括39项治疗试验。 2016年至2021年间，15项研究 UFHCC 成员的研究结果通过实验室科学家/临床转化为临床试验（UFHCC 13 项）研究者合作。自 2016 年以来，CTHR 临床研究人员招募了 1,199 名患者进行治疗试验， 2021 年，299 名患者中的 174 名参加了 UFHCC 治疗试验。为了加速临床研究，自 2019 年，UFHCC 向 CTHR 招募了 8 名临床研究人员，并提供有保障的时间和资源来开发 IIT。 CTHR 导师培养了194名研究生和92名博士后，其中44%是女性；〜10% 代表性不足的少数群体 (URM)。 NIH 培训支持了 25 名学员（12 名女性；5 名 URM）补助金。 CTHR 领导层和成员致力于通过招聘来增强多样性的计划与多元化、公平和包容性副总监合作。未来计划，与 UFHCC 保持一致战略计划，包括转化免疫学、微生物组和致癌作用方面的招募、P01 拨款（例如，脑、微生物组、肺），并有针对性地招募临床研究人员（例如女性、肺、血液）。