Cancer Therapeutics and Host Response Research Program

癌症治疗和宿主反应(CTHR)计划 佛罗里达大学健康癌症中心(UFHCC)CTHR计划将具有专业知识的研究人员整合在一起 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 来推进癌症的治疗。CTHR由免疫肿瘤学专家Sayour和权威专家Jobin领导 微生物群与癌症的关系。该中心由7所高校19个系的62名成员组成，其中包括19所学院 自2016年以来招募的成员。CTHR成员支持1)定义癌症免疫生物学的科学目标 并开发新的免疫疗法；2)阐明微生物组在癌症发生和治疗中的作用； 3)确定涉及关键癌症途径的新的靶向治疗；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设施启用的泛癌症平台进行投资 用于多种新的免疫疗法；ii)启动首个人类信使核糖核酸纳米颗粒疫苗试验 (NCT04573140)；iii)FDA IND批准用于治疗CD70+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反应性 临床前肺模型；以及，v)发现和开发新的治疗化合物，包括络合物 来自海洋生物的细胞毒分子和合理设计的针对bclxl的PROTAC，目前处于I期临床 审判。该计划通过IIT智库将基本发现转化为临床。CTHR有一个同行- 审查直接成本为910万美元/年的供资基础(自2019年以来增长23%)，代表72个同行审查的项目， 其中27项来自NCI(320万美元的直接成本)，包括13项MPI奖。自2016年以来，CTHR成员产生了 1,276篇与癌症相关的出版物，24%有影响因素&>10，其中38%是规划内的，32% 跨计划的，67%的多机构。临床医生与基础或联合出版的百分比 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 启动41项机构干预试验，包括39项治疗试验。2016至2021年间，15项研究 UFCC成员的发现通过实验室科学家/临床转化为临床试验(UF的13项) 调查员之间的合作。自2016年以来，CTHR临床研究人员招募了1199名患者进行治疗试验， 并在2021年招募了299名UFHCC治疗试验患者中的174名。为了加快临床研究，自 2019年，UFCC招募了8名临床研究人员到CTHR，并保护了时间和资源来开发IITs。CTHR 导师培养了194名研究生和92名博士后实习生，其中44%是女性；~10% 代表不足的少数族裔(URM)。有25名学员(12名女性；5名城市管理人员)接受了国立卫生研究院的培训 资助金。CTHR领导层和成员致力于通过在#年招聘来加强多样性的计划 与负责多样性、公平和包容性的协理主任结成伙伴关系。未来计划，与UFCC保持一致 战略计划，包括在翻译免疫学、微生物组和致癌方面的招聘，P01赠款(例如， (例如，脑、微生物组、肺)和有针对性地招募临床研究人员(例如，妇女、肺、血液)。

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).