SAVALnet – Science and Medicine

When the immune system encounters foreign antigens (parts of pathogens or tumors), it attempts to recognize and neutralize them. Epitopes are parts of these antigens that the immune system “sees” and recognizes as targets of the immune response.

Although chimeric antigen receptor (CAR) T cells and monoclonal antibodies have shown great promise in treating hematological malignancies by targeting antigens on rogue cells, their use in acute myeloid leukemia (AML) is hampered by the lack of specific markers. With tumor. This carries the risk of damaging healthy cells and tissues during treatment.

Researchers in Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Introduce a genetic change in hematopoietic stem/progenitor cells (HSPCs) that allows them to survive during immunotherapy for acute myeloid leukemia.

Epitope engineering, specifically the editing of donor-derived hematopoietic stem/progenitor cells (HSPCs) for use in bone marrow transplants, is a potential solution to this challenge. Modification of specific genes in HSPCs, such as FLT3, CD123, and KIT, altered epitope marks without altering the normal function of the genes.

This approach can increase the safety and effectiveness of treatment by more effectively targeting cancer cells, sparing healthy cells and reducing harmful side effects.

Released 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 hematological malignancies, and possibly to non-genotoxic conditioning of non-malignant diseases.

Outside the scope of the study is the cost of personalized medicine. Currently, CAR T-cell therapy alone can cost more than $1 million. Although the introduction of epitope gene editing could raise the cost, it will offset this cost if it makes overall investments in CAR T-cell therapy safer and more effective.