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计划将研究人员与专业知识相结合在微生物组，免疫学，癌症生物学，生物工程，药物化学和临床试验开发中推进癌症治疗。 CTHR由免疫肿瘤学专家Sayour和权威的Jobin领导关于微生物组和癌症。 CTHR由来自7所大学的19个部门的62名成员组成，其中包括19个自2016年以来招募的成员。CTHR成员支持科学目的1）定义癌症免疫生物学并发展出新颖的免疫疗法； 2）阐明微生物组在癌症发展和治疗剂中的功能； 3）确定吸引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。该计划的关键进展包括i）在CGMP设施中投资启用Pan-Cancer平台用于多种新型免疫疗法； ii）首次人类mRNA-纳米颗粒疫苗试验的启动（NCT04573140）; iii）FDA IND批准对CD70+恶性肿瘤进行创新的CAR-T； iv）新发现来自免疫治疗反应性非小细胞肺癌患者的微生物组赋予了反应性在临床前肺模型中； v）发现和开发新的治疗化合物，包括复杂的化合物来自海洋生物的细胞毒性分子和针对BCL-XL的合理设计的Protac，现在在I期临床上审判。该计划通过IIT智囊团将基本发现转化为诊所。 CTHR具有同行审查的资金基础> 910万美元/年的直接成本（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（320万美元的直接费用），其中包括13个MPI奖项。自2016年以来，CTHR成员产生了 1,276个与癌症相关的出版物，有24％的影响因素> 10，其中38％是概括性的，32％编程间和67％的多机构。临床医生与基本或人口科学家几乎翻了一番，达到59％。 CTHR成员获得了39家新专利。自2016年以来，CTHR 启动了41项机构介入试验，包括39次治疗试验。在2016年至2021年之间，15个研究 UFHCC成员的发现通过实验室科学家/临床将临床试验转化为临床试验（UF）研究者合作。自2016年以来，CTHR临床研究人员招募了1,199名患者接受治疗试验，在2021年，在299名患者中，有174名参加了UFHCC治疗试验。加速临床研究，因为 2019年，UFHCC招募了8名临床研究人员，以使用受保护的时间和资源来开发IIT。 CTHR 导师培训了194名研究生和92名博士后学员，其中44％是女性；〜10％代表性不足的少数民族（URM）。 NIH培训支持25名学员（12名女性； 5个URM）赠款。 CTHR领导力和成员致力于通过招募来增强多样性的计划与多样性，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，P01赠款（例如，大脑，微生物组，肺），并有针对性地招募临床研究者（例如，女性，肺，血液）。