THE PROBLEM

Recent advances in chimeric antigen receptor (CAR) T cell therapy have shown promise in eliminating cells that express specific surface antigens, such as CD19 in B cell neoplasms. However, this approach has significant limitations:

1. Lack of Discrimination: CAR T cell therapy targeting CD19 does not differentiate between normal and malignant B cells, resulting in prolonged B cell aplasia, which can lead to serious complications.
2. Toxicity to Normal Cells: For most malignancies, including acute myeloid leukemia (AML), normal cells share antigens with cancerous cells (e.g., AML antigens are present on normal myeloid progenitors). Consequently, targeting these antigens can cause toxicity to the normal myeloid system.
3. Relapse in AML: Despite aggressive therapies, most AML patients experience relapse, indicating a need for more effective strategies that can target the disease without compromising normal hematopoiesis.
4. Transient CAR T Cells: Current strategies aimed at producing transient CAR T cells to mitigate long-term toxicity may undermine the therapy's ability to provide lasting immune surveillance against tumors.