KG2032 acknowledges a subset of polymorphic HLA-DRB1 molecules. KG2032 acknowledges a subset of polymorphic HLA-DRB1 molecules. Credit score: Nature Most cancers (2025). DOI: 10.1038/s43018-025-00934-1
One most important purpose of anti-cancer therapies is to kill tumor cells with out affecting the encompassing regular cells. Due to this fact, many medicine are designed to focus on tumor-specific antigens, that are molecules solely expressed by most cancers cells. Nonetheless, it has confirmed tough to establish such particular antigens in sure most cancers varieties, together with acute myeloid leukemia (AML).
AML sufferers are sometimes handled utilizing allogeneic hematopoietic stem cell transplantation (allo-HCT), the place they obtain stem cells from a donor. Sadly, regardless of developments with allo-HCT, many AML sufferers relapse.
In an article printed in Nature Most cancers, a multi-institutional analysis workforce led by the College of Osaka describes how a molecule known as HLA-DRB1 can be utilized as a goal for chimeric antigen receptor (CAR)-based remedy for AML.
In CAR-based remedy, T cells are engineered to focus on and kill cells that specific a particular molecule. CAR T cells have been extremely profitable in people with B cell leukemia/lymphoma and a number of myeloma (MM). Nonetheless, a lot of the CAR T cell targets presently in scientific trials for AML are additionally expressed in regular cell varieties, resulting in potential toxicity.
“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,” says Shunya Ikeda, lead writer of the examine. “We aimed to use that same strategy to find AML-specific antigens.”
The workforce started screening 1000’s of mAbs raised in opposition to AML cells, narrowing this listing right down to 32 that bind particularly to AML cells. One mAb, named KG2032, clearly sure to AML cells in over 50% of affected person samples examined. Utilizing a sequencing technique, the researchers decided that KG2032 sure to HLA-DRB1.
“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,” explains Naoki Hosen, senior writer of the article.
“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 discovering signifies that HLA-DRB1 could be a potential goal in treating sure sufferers with AML who’ve relapsed after allo-HCT.
The workforce then engineered KG2032 CAR T cells with out the reactive HLA-DRB1 allele to check this discovering. The KG2032 CAR T cells displayed robust and particular anti-AML results in vitro with cell tradition experiments, in addition to in vivo with a mouse mannequin. The handled mice didn’t show any overt indicators of toxicity. Engineered wire blood-derived CAR pure killer (NK) cells confirmed comparable outcomes.
Total, these very promising findings point out that KG2032-derived CAR T or NK cells could also be a lifesaving intervention for AML sufferers who’ve relapsed following allo-HCT. Scientific trials are presently being deliberate for each cell varieties.
Extra data:
Shunya Ikeda et al, CAR T or NK cells concentrating on mismatched HLA-DR molecules in acute myeloid leukemia after allogeneic hematopoietic stem cell transplant, Nature Most cancers (2025). DOI: 10.1038/s43018-025-00934-1
Offered by
Osaka College
Quotation:
HLA-DRB1 molecule affords potential goal for CAR remedy in relapsed acute myeloid leukemia post-transplantation (2025, April 2)
retrieved 3 April 2025
from https://medicalxpress.com/information/2025-04-hla-drb1-molecule-potential-car.html
This doc is topic to copyright. Aside from any honest dealing for the aim of personal examine or analysis, no
half could also be reproduced with out the written permission. The content material is supplied for data functions solely.
