- Aim 1. Elucidate Principles of Cancer Immunobiology to Develop Novel Immunotherapies for Refractory Malignancies.
CTHR members explore tumor immunobiology and mechanisms of immune evasion that can be exploited to develop novel and effective immunotherapeutic strategies targeting refractory malignancies. Examples include mechanistic understanding of hematopoietic stem cell/tumor interplay, tumor immuno-metabolomics, immune/tumor cell engagement within the microenvironment, and therapeutic modalities to augment anti-tumor immunity (e.g., mRNA vaccine, CAR-T, DC vaccines, combinational therapies).
- Aim 2. Define Microbiome Function in Cancer Development and Therapeutics.
CTHR members investigate how bacterial metabolites affect anti-tumor immunity, how bacteria modulate carcinogenesis through inflammation, genotoxin production, and immunosuppression. They also study how microorganisms affect therapeutic response through drug metabolism and interactions with the immune system and translate findings into studies of the complications of HSCT, such as GVHD and infection. These studies are facilitated by the creation of the UFHCC Microbiome Cancer Biobank.
- Aim 3. Discover and Develop Targeted Therapeutics Engaging Key Cancer Pathways.
CTHR members discover antineoplastic properties of natural products, identify new “druggable” targets, and develop synthetic compounds that interact with key cancer pathways to guide new clinical trials to address CA priority cancers. Examples include STAT3 inhibitors, senolytic agents, and BCL-XL and HDAC degraders.
- Aim 4. Translate Scientific Discoveries into Early Phase Clinical Trials.
Engaging members in all 3 UFHCC programs through disease group mini retreats, program meetings, and the I2T3, discoveries ranging from screening interventions to new therapy combination concepts and formulating first-in-human trials.
- Across all aims, translation of CTHR discoveries is facilitated by collaboration among members across programs. Candidates for clinical development are evaluated in collaboration between the member and the ADs for Basic Sciences, Translation & Innovation, and Clinical Research, and further discussed by regular I2T3 meetings. The latter includes stakeholders (e.g., clinical and laboratory scientists, Citizen Scientists, COE) and centralized infrastructure to support statistical rigor (BCB-SR), inclusive patient populations (COE), and preparation of FDA IND/IDE applications for novel clinical trial protocol development provided by the CRO.
