Funding Opportunity Number: RFA-AG-24-046
Deadlines
Letter of Intent: January 7, 2024
Submission: February 7, 2024
Award Amount: Up to $5,000,000.
Background
Chimeric antigen receptor cell therapy has emerged in recent years as a breakthrough in cancer treatment. A CAR is a receptor protein engineered to allow immune cells, typically T cells (CAR-T), to target surface antigens independent of the human leukocyte antigen. CAR engineering combines the antigen-binding domain of an antibody and T cell receptor (TCR) activating functions into a single chimeric receptor. CAR-T cell therapy revolutionized cancer treatment, especially hematologic malignancies.
There is growing interest in adopting CAR approaches to modify the aging process as well as the onset and progression of neurodegenerative diseases. A potential target for CAR approaches may include senescent cells, which are cells in a state of permanent growth arrest that show a loss of proliferation or regeneration capacity, altered metabolism, resistance to apoptosis, and secretion of pathogenically active molecules. Senescent astrocytes, microglia, neurons, and endothelial cells have been detected in the brains of AD patients and AD animal models. It has been shown that removing senescent cells ameliorates A? and Tau protein pathology and improves memory in AD model mice. Indeed, in proof-of-concept experiments, it has been demonstrated that CAR-T cells can be effective senolytic agents.
Research Objectives and/or Scope
The goal of this NOFO is to support a proof-of-principle approach and address the question of whether novel immunotherapeutic approaches for cancer based on CAR-T cells and/or CAR-M/NK cells could be repurposed as treatment modalities for AD/ADRD.
For more detailed information, please see the funding announcement website.