Cancer Therapeutics and Host Response Research Program

CANCER THERAPEUTICS AND HOST RESPONSE (CTHR) PROGRAM 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 therapy 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% interprogrammatic, 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. There were 25 trainees supported by NIH training grants. 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., gynecological oncology, breast, lung, blood)