Cancer Therapeutics and Host Response Research Program

癌症治疗和宿主反应研究计划

• 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
• 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

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）研究：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 微生物组学、免疫学、癌症生物学、生物工程、药物化学和临床试验开发 来推进癌症治疗。CTHR由免疫肿瘤学专家萨尤和权威乔宾领导 微生物组和癌症。CTHR由来自7所学院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成员支持以下科学目标：1）定义癌症免疫生物学 和开发新的免疫疗法; 2）阐明微生物组在癌症发展和治疗中的功能; 3)确定参与关键癌症途径的新靶向疗法;以及，4）将发现转化为新的临床 审判该计划的主要进展包括i）对cGMP设施的投资使泛癌症平台成为可能 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 （NCT 04573140）; iii）FDA IND批准针对CD 70+恶性肿瘤的创新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;和，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的合理设计的PROTAC，目前处于I期临床试验阶段。 审判该计划通过IIT智库将基本发现转化为临床。CTHR有个同行- 审查了直接成本> 910万美元/年的资金基础（自2019年以来增长了23%），代表了72个同行评审项目， 其中27个来自NCI（320万美元的直接成本），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%为项目内出版物，32%为项目内出版物。 67%是跨部门的，67%是跨机构的。临床医生与基础或 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，包括39项治疗试验。在2016年至2021年期间，15项研究 来自UFHCC成员的研究结果通过实验室科学家/临床 调查员合作。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名患者中有174名参加了UFHCC治疗试验。为了加速临床研究， 2019年，UFHCC招募了8名临床研究者到CTHR，并保护时间和资源来开发IIT。CTHR 导师培训了194名研究生和92名博士后实习生，其中44%是女性; ~10% 代表性不足的少数民族（URM）。有25名受训人员（12名妇女; 5名统一资源管理人员）得到国家卫生研究所培训的支助 赠款。CTHR领导层和成员致力于通过招聘来增强多样性的计划， 与多样性，公平和包容副主任的伙伴关系。与UFHCC保持一致的未来计划 战略计划，包括翻译免疫学，微生物组和致癌作用的招聘，P01赠款（例如， 脑、微生物组、肺），以及有针对性地招募临床研究者（例如，妇女的肺、血液）。