Engineered type 1 regulatory T cells designed for clinical use kill primary pediatric acute myeloid leukemia cells.

Engineered type 1 regulatory T cells designed for clinical use kill primary pediatric acute myeloid leukemia cells. Haematologica. 2020 Sep 28;Online ahead of print: Authors: Cieniewicz B, Uyeda MJ, Chen PP, Sayitoglu EC, Liu JM, Andolfi G, Greenthal K, Bertaina A, Gregori S, Bacchetta R, Lacayo NJ, Cepika AM, Roncarolo MG Abstract Type 1 regulatory (Tr1) T cells induced by enforced expression of IL-10 (LV-10) are being developed as a novel treatment for chemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft vs host disease while mediating graft vs leukemia (GvL) effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature. Overlaying the signatures of sensitive and resistant pAML onto the public NCI TARGET pAML dataset revealed that sensitive pAML clustered with M5 monocytic pAML and pAML with MLL rearrangement. Resistant pAML clustered with myelomonocytic leukemias and those bearing the core binding factor translocations inv(16) or t(8;21)(RUNX1-RUNX1T1). Furthermore, resistant pAML upregulated the membrane glycoprotein CD200, which binds to the ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research