Engineered Neutrophils for Intratumoral Delivery and Targeting
Abstract
Therapies that modulate the immune system have shown great promise for treatment of cancer in the past decade. However, there are still barriers to overcome to realize their full potential against solid tumors, including renal cell carcinoma (RCC). The major hurdle to overcome is that tumor cells are able to produce factors that thwart the immune cells that these therapies target. In our proposed studies, we investigate the potential for using a specific type of innate immune cell called a neutrophil as a vehicle to deliver factors that re-activate the cancer fighting activities of immune cells within the tumor. Our proposed research will address the following KCRP Focus Area: Develop novel therapeutic strategies for the treatment of kidney cancer, such as novel drug targets, therapeutic modalities and agents, treatment combinations and drug delivery systems. Neutrophils are the foot soldiers of the innate immune system and are typically present in abundance wherever inflammation occurs, including at tumor sites. Our research team has extensive expertise in studying neutrophils. We recently developed a precursor cell line that when injected into mice has the ability to take up residence in the bone marrow (where most immune cell development occurs) and produce large numbers of neutrophils. We call this new cell line a Neutrophil Progenitor (NP) and we have further shown that we can alter its activity using standard genetic engineering techniques. The discovery of NPs that can be maintained and modified in the laboratory opened up new avenues to investigate whether they can be altered so that they can treat disease. In our proposed study, we take advantage of the fact that neutrophils normally travel from the bone marrow to sites of RCC tumors. Our goal is to genetically modify NPs so that when are injected into tumor-bearing mice, they produce neutrophils that will travel to RCC tumors and release factors that directly and indirectly cause the tumor cells to die or prevent them from metastasizing. If successful in an experimental animal model, future work will aim to translate our findings to humans and the eventual treatment of kidney cancer patients with a cell therapy based on NPs. Given the barriers that the RCC tumor presents to current therapies, this project has the potential for high impact to advance kidney cancer research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310824
Entities
People
- Craig Lefort
Organizations
- Rhode Island Hospital
- United States Army