City of Hope® Research Spotlight features the latest research defining the future of medical treatment. This first roundup highlights a T cell engager that shows promise as a novel treatment for acute myeloid leukemia, findings linking immune aging to thymic involution and a potential way of eliminating myeloma with weak antigen expression.
To learn more about research at City of Hope, visit the Research & Innovation page.
IL1RAP-Specific T Cell Engager Depletes Acute Myeloid Leukemia Stem Cells
The novel anti-IL1RAP/CD3 T cell engager (TCE) BIF002 effectively targets and eliminates leukemic stem cells (LSCs) and bulk blasts in acute myeloid leukemia (AML) without harming normal hematopoietic stem cells (HSCs), showing significant potential as a new treatment for AML, according to a Journal of Hematology and Oncology study. Interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on AML bulk blasts and LSCs, but not on normal HSCs — offering a unique therapeutic target. Researchers, led by Guido Marcucci, M.D., professor and chair, along with Bin Zhang, Ph.D., and Lucy Ghoda, Ph.D., of the Department of Hematologic Malignancies Translational Science at Beckman Research Institute of City of Hope, and working closely with the IDDV-supported, Antibody Generate Engine led by John Williams, Ph.D., and Miso Park, Ph.D., Department of Cancer Biology and Molecular Medicine, isolated antibodies to IL1RAP from CD138+ B cells collected from immunized mice through optoelectric positioning and single-cell sequencing. They produced and characterized individual mouse monoclonal antibodies (mAbs), from which they developed BIF002, an anti-human IL1RAP/CD3 TCE using Fab arm exchange. The antileukemic activity of BIF002 was characterized both in vitro and in vivo, utilizing multiple cell lines and patient-derived AML samples. This TCE showed potent efficacy in vitro and in vivo, effectively activating T cells to target and destroy IL1RAP-expressing leukemic cells at very low concentrations, with the effect dependent on effector-to-target ratios. The novel anti-IL1RAP/CD3 TCE, BIF002, was shown to eradicate LSCs and significantly prolong survival of AML xenografts, representing a promising, novel treatment for AML.
