2023-09-07 03:01:03
When the immune system encounters foreign antigens (parts of pathogens or tumors), it tries to identify and neutralize them. Epitopes are the parts of these antigens that the immune system “sees” and recognizes as targets of an immune response.
Although chimeric antigen receptor (CAR) T cells and monoclonal antibodies have shown great promise in the treatment of blood malignancies by targeting rogue cell antigens, their use in acute myeloid leukemia (AML) ) is hampered by the lack of tumor-specific markers. This carries the risk of damaging healthy cells and tissues during treatment.
researchers of the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston introduced a genetic alteration into donor hematopoietic stem/progenitor cells (HSPCs) that allows them to survive immunotherapy treatment for acute myeloid leukemia.
Epitope engineering, specifically editing hematopoietic stem/progenitor cells (HSPCs) obtained from a donor for use in bone marrow transplantation, is a potential solution to this challenge. Modifying specific genes in HSPCs, such as FLT3, CD123, and KIT, changed the epitope tags without altering the normal function of the genes.
This approach could increase the safety and effectiveness of the treatment, since it would more effectively target cancer cells, sparing healthy ones, and reducing harmful side effects.
The edited epitopes cause the loss of specific antibody binding sites, rendering cells resistant to CAR T cells and monoclonal antibodies without affecting their physiological expression, regulation, and intracellular signaling.
The authors suggest that it could be applied not only to AML, but also to other hematologic malignancies, and potentially to non-genotoxic conditioning for non-malignant diseases.
Beyond the scope of the study is the cost of personalized medicine. Currently, CAR T cell treatment alone can cost more than a million dollars. Although the introduction of an epitope gene-editing method could add to the cost, this expense would be offset by making overall investments in CAR T-cell therapy safer and more effective.
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