04 March 2024

A newly designed T cell engager antibody could become an effective treatment for patients with acute myeloid leukaemia (AML) who do not qualify for stem cell transplants, researchers have reported.

The treatment aims to counter the effects of the protein CD38, which suppresses the immune system and whose production is stimulated by type 2 interferon (IFNγ).

Scientists at City of Hope Hospital, Duarte, California, USA, have reported their findings in Blood, based upon experiments in the lab and in mouse models of AML.

The antibody they have designed, called ‘CD38-BIONIC’, makes a bridge between T cells and leukaemia cells that express CD38. As well as killing these cells, this also leads to increased production of  IFNγ, which in turn increases CD38 expression on previously CD38-negative cells, such as leukaemia stem cells. This ‘unmasking’ of the cells enables the immune system to kill them off.

Study co-leader Professor Flavia Pichiorri said: “CD38 has successfully been exploited as a therapeutic target in multiple myeloma and other forms of leukaemia.

“Because AML stem cells are mainly CD38-negative, however, scientists have not prioritised CD38 as a therapeutic target for relapsed acute myeloid leukaemia.”

Fellow co-leader Professor John Williams said: “We believe that the compact format of BIONIC leads to an efficient immune system connection point with the CD38-positive blast, which drives IFNγ production. The leukaemia stem cells react to the IFNγ, painting themselves with CD38, which in turn allows them to be targeted by the CD38-CD3 BIONIC.”


Murtadha M, Park M, Zhu Y, Caserta E, Napolitano O, Tandoh T, Moloudizargari M, Pozhitkov A, Singer MK, Dona AA, Vahed H, Gonzalez A, Ly K, Ouyang C, Sanchez J, Nigam L, Duplan A, Chowdhury A, Ghoda LY, Li L, Zhang B, Krishnan AY, Marcucci G, Williams JC, Pichiorri F. (2024) “CD38-directed, single-chain T cell-engager targets leukemia stem cells through IFNγ-induced CD38 expression.” Blood, doi: 10.1182/blood.2023021570

Link: https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2023021570/515073/CD38-directed-single-chain-T-cell-engager-targets

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