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 (IFN纬).
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 鈥楥D38-BIONIC鈥�, 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 听IFN纬, which in turn increases CD38 expression on previously CD38-negative cells, such as leukaemia stem cells. This 鈥榰nmasking鈥� of the cells enables the immune system to kill them off.
Study co-leader Professor Flavia Pichiorri said: 鈥淐D38 has successfully been exploited as a therapeutic target in multiple myeloma and other forms of leukaemia.
鈥淏ecause AML stem cells are mainly CD38-negative, however, scientists have not prioritised CD38 as a therapeutic target for relapsed acute myeloid leukaemia.鈥�
Fellow co-leader Professor John Williams said: 鈥淲e believe that the compact format of BIONIC leads to an efficient immune system connection point with the CD38-positive blast, which drives IFN纬 production. The leukaemia stem cells react to the IFN纬, painting themselves with CD38, which in turn allows them to be targeted by the CD38-CD3 BIONIC.鈥�
Source:
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) 鈥淐D38-directed, single-chain T cell-engager targets leukemia stem cells through IFN纬-induced CD38 expression.鈥� Blood, doi: 10.1182/blood.2023021570
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