Sharma receives James and Esther King Biomedical Research Program grant

Congratulations to Dr. Blanka Sharma, assistant professor in the J. Crayton Pruitt Family Department of Biomedical Engineering, who received a $1.23 million award from the Florida Department of Health James and Esther King Biomedical Research Program for her joint grant titled Nanoparticle-based targeting of miR183 for immunotherapy of lung cancer.

Sharma who is the co-prinicpal investigator is working with Dr. Julie Djeu, professor and associate center director, Moffit Cancer Center, who is the principal investigator. The proposed research will offer a new approach to lung cancer immunotherapy that has never been tried before.

Djeu’s research interest includes identification of novel targets that can modulate inflammatory pathways to prevent and treat cancer. Circulating immune cells function to survey the body for abnormal cells and a type of immune cells, called natural killer (NK) cells are especially potent in seeking out tumor cells through multiple receptors that only bind unique proteins that appear on nascent tumor cells. These receptors utilize a key protein called DAP12 to anchor to the NK cell surface. However, they found that tumor cells produce a protein called transforming growth factor-b that can disrupt NK cell function by depleting DAP12.  This is accomplished by activation of a microRNA, miR183 that specifically binds to the DAP12 gene to destroy it. Therefore NK cells cannot display their receptors on the cell surface and become blind to the surrounding tumor cells, allowing tumor cells to escape immune detection.

Djeu’s team also found that nicotine from tobacco smoke, long associated with lung cancer development, can activate the same mechanism in NK cells. Without immunity, cancer cells can grow unchecked. This is the first report of a microRNA that controls immune cells in lung cancer and the targeting of this microRNA presents a highly innovative and new strategy to treat cancer.

Sharma’s research interests are in the design of targeted drug delivery systems for applications is regenerative medicine and cancer therapy. Sharma’s team is working on the development of nanoparticles to deliver agents that block miR183 and reactivate NK cell tumoricidal function and destroy lung tumors.  Sharma’s team will engineer the nanoparticles with novel NK cell homing molecules to reach NK cells in the tumors and delivery the anti-miR183. 

The James and Esther King Biomedical Research grant will enable them to study this therapeutic strategy in humanized mouse models of lung cancer and biomimetic in vitro models of human lung tumors, to provide a foundation for future clinical application. Several advantages are associated with such nanoparticles. They can serve as off-the-shelf reagents and it can be administered not only to any lung cancer patient, but also to patients of other tumor types. It is well accepted that immune escape is a hallmark of all cancers and our product could be a universal anti-cancer agent. If efficacy is demonstrated with these nanoparticles, this method would revolutionize the treatment of lung cancer.

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