UF Health Cancer Center awards pilot grants for cancer targeting and therapeutics projects

Two UF Health Cancer Center researchers have been awarded pilot funding for promising projects to advance innovative cancer therapeutics through developing small-molecule drugs and enhancing immunotherapy.

The pilot funding was awarded to Yufeng Xiao, Ph.D., and Haipeng Tao, M.D., Ph.D., who conduct research through the center’s Cancer Targeting and Therapeutics research program. Harnessing the drug discovery strengths at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, the research program aims to accelerate the discovery, development, and clinical translation of targeted small molecule and bio-therapies.

The new projects are designed to collect preliminary data required to test novel ideas with the goal of creating a foundation for larger studies. Learn more about the research projects below.

“Development of chaperone-targeting chimeras (ChaTACs) as novel therapeutics for targeted protein degradation”

Yufeng Xiao, Ph.D.
Assistant Scientist
Department of Medicinal Chemistry, UF College of Pharmacy

Yufeng
Yufeng Xiao, Ph.D.

Proteolysis-targeting chimera, or PROTAC, is an emerging approach to eliminating proteins that cause cancer cells to grow. However, current PROTACs face challenges such as limited tissue selectivity and the potential development of cancer resistance.

Xiao and his research team are expanding this strategy by targeting another protein, called heat shock protein 90, or HSP90, that’s essential for cancer cell survival, to induce targeted protein degradation.

The researchers plan to design and test a new type of molecule called a chaperone-targeting chimera, or ChaTAC, that can bind to both HSP90 and oncoprotein BCL-XL/BCL-2. By bringing these two proteins together, the ChaTAC may trigger the degradation of BCL-XL and BCL-2, which are important for cancer cell survival. Notably, cancer cells have higher levels of active HSP90 than normal cells, so the ChaTACs may preferentially target and kill cancer cells.

The researchers have already designed and tested some initial BCL-ChaTAC molecules, which have shown promising effects at killing cancer cells and fewer side effects than a related drug.

Further development and evaluation of the ChaTACs could lead to new, more effective and selective cancer treatments. This platform can also be applied to other cancer targets, which represents a valuable new approach in the field of targeted protein degradation, the researchers said.

“Enhancing Cancer Treatment: Synergistic Effects of 3-in-1 CAR T-Cells and PD-1 Blockade”

Haipeng Tao, M.D., Ph.D.
Assistant Scientist
Lillian S. Wells Department of Neurosurgery, UF College of Medicine

Haipeng Tao, M.D., Ph.D.

This project will test a novel CAR T-cell therapy that aims to improve the effectiveness of cancer immunotherapy, especially for difficult-to-treat cancers like glioblastoma.

In glioblastoma and certain other cancers, cells called tumor-associated macrophages make up to 50% of a tumor’s mass, playing a pivotal role in dampening the immune response and negatively affecting patient survival. Targeting these cells is a promising strategy to overcome the limitations of current cancer treatments.

The researchers will focus on the leukocyte-associated immunoglobulin-like receptor 1, or LAIR1, which is prominently expressed on these cells and is crucial to their immunosuppressive function.

The study will evaluate the antitumor effectiveness of a new CAR platform, which combines three critical functions: precise tumor targeting, enhanced CAR T-cell tumor trafficking/penetrating, and inhibition of tumor-associated macrophages through blocking LAIR1 signaling. The study also holds potential for treating other tumors that express LAIR1, such as lung, ovarian, and breast cancers, the researchers said.

“This innovative 3-in-1 CAR T-cell therapy, developed by our team, works synergistically with PD-1 blockade, which benefits only a fraction of cancer patients, and may dramatically improve outcomes for aggressive cancers,” Tao said. “I’m excited to see how this strategy can transform cancer therapeutics.”


The UF Health Cancer Center’s pilot funding programs receive crucial support from the state of Florida through the Casey DeSantis Cancer Research Act (Fla. Stat. § 381.915).

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