Childhood Cancer

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Immuno-therapeutic Targeting of CD56 in CBA2T3/GLIS2-AML in Children

Fred Hutchinson Cancer Research Center
Soheil Meshinchi, MD/PhD
Grant Type: 
Reach Grants
Year Awarded: 
Type of Childhood Cancer: 
Acute Myeloid Leukemia (AML)
Project Description: 

Co-investigator: Dr. Colin Correnti

Acute myeloid leukemia (AML) is a particularly devastating disease in infants, where therapies that are intended to cure leukemia frequently fail to cure the disease and lead to significant life-limiting or life-ending complications. Leukemia-specific targeted therapies are critical especially in these most vulnerable patients in order to cure the disease without causing irreversible damage to their growing body. Through the largest and most detailed sequencing studies, we have identified a genetic abnormality that is only seen in children younger than 3 years of age. This genetic alteration called CBF/GLIS causes a lack of response to all available therapies, and more than 80% of babies with this mutation die of leukemia despite receiving intensive chemotherapy. We have discovered that leukemic cells in babies with CBF/GLIS express a protein called CD56 at high levels. Expression of this protein on the leukemia cells provides an opportunity for targeting the leukemic cells with immunotherapy. Fortunately, one such immunotherapy (called antibody-drug conjugates; CD56-ADCs) has been developed for other diseases that can be repurposed for use in AML. We can also create new immunotherapies against CD56.

Project Goal
In this project, we will test the ability of available CD56-ADCs to kill CBF/GLIS-positive AML cells as well as create a novel immunotherapy, called bi-specific (BITE) or multi-specific immunotherapies, against CD56. We are highly optimistic that given the high CD56 expression on leukemic cells, we can rapidly identify or create new immunotherapies for infants with high-risk AML.

Co-funded by: 
Cure4Cam Childhood Cancer Foundation