CAR-T Therapy for AML: A New Hope
- Osaka, japan - A multi-institutional team, spearheaded by The University of Osaka, has pinpointed a molecule, HLA-DRB1, as a promising target for chimeric antigen receptor (CAR)-based therapy in...
- The CAR therapy approach involves modifying T cells to recognize and eliminate cells expressing a specific molecule.
- Shunya Ikeda,lead author,explained their strategy: "In our previous work in MM,we screened monoclonal antibodies (mAbs) to identify any that could react with human MM samples but not with...
Scientists have identified HLA-DRB1 as a new, promising target for CAR-T therapy in acute myeloid leukemia (AML), offering a potential breakthrough for patients facing relapse after allogeneic hematopoietic stem cell transplantation. This innovative approach, spearheaded by The University of Osaka, involves modifying T cells to specifically target and eliminate AML cells, addressing a critical need in CAR-T treatment. KG2032 CAR T cells showed strong anti-AML effects in laboratory and animal models, paving the way for crucial advancements. News Directory 3 is following this story closely. Clinical trials are on the horizon for KG2032-derived CAR T and NK cells. Discover what’s next in the fight against AML.
New Target Discovered for acute Myeloid Leukemia Therapy
Updated June 24, 2025
Osaka, japan – A multi-institutional team, spearheaded by The University of Osaka, has pinpointed a molecule, HLA-DRB1, as a promising target for chimeric antigen receptor (CAR)-based therapy in acute myeloid leukemia (AML).This offers renewed hope for patients who relapse following allogeneic hematopoietic stem cell transplantation (allo-HCT),a common treatment where patients receive donor stem cells.
The CAR therapy approach involves modifying T cells to recognize and eliminate cells expressing a specific molecule. While CAR T-cell therapies have demonstrated success in treating B-cell leukemia/lymphoma and multiple myeloma, current AML targets often lead to toxicity due to expression in normal cells.
Shunya Ikeda,lead author,explained their strategy: “In our previous work in MM,we screened monoclonal antibodies (mAbs) to identify any that could react with human MM samples but not with normal blood cells. We aimed to use that same strategy to find AML-specific antigens.”
The team screened thousands of mAbs against AML cells, narrowing the field to 32 that selectively bind to AML cells. One mAb, KG2032, stood out, binding to AML cells in over half the patient samples tested. Further inquiry revealed that KG2032 targets HLA-DRB1.
Naoki Hosen, senior author, noted the specificity: “Interestingly, we found that KG2032 reacted with a specific HLA-DRB1 subset in which the protein has an amino acid other than aspartic acid in the 86th position. KG2032 would therefore only be reactive to AML cells in individuals with mismatched HLA-DRB1, meaning the patient carries this amino acid residue but the allo-HCT donor does not.” This specificity is key to minimizing toxicity in healthy cells, a major challenge in acute myeloid leukemia (AML) treatment.
To validate their findings, the team engineered KG2032 CAR T cells lacking the reactive HLA-DRB1 allele. These modified cells exhibited potent and specific anti-AML effects in laboratory experiments and in a mouse model, without causing noticeable toxicity. Similar results were observed with engineered cord blood-derived CAR natural killer (NK) cells.
What’s next
These findings suggest that KG2032-derived CAR T or NK cells could provide a life-saving intervention for AML patients relapsing after allo-HCT. Clinical trials are in the planning stages for both cell types, marking a critically important step forward in targeted therapies for acute myeloid leukemia (AML).