279 ILT3 blockade reduces tumor blast cells in acute myeloid leukemia PBMC and inhibits tumor cell growth in a humanized AML tumor model

Background Immunoglobulin-like transcript 3 (ILT3), an immune-inhibitory receptor expressed on myeloid cells, is highly in acute leukemia (AML) with monocytic differentiation (M4 and M5 subtypes) clinically negatively correlated overall survival. We examined the effects of a selective potent chimeric anti-ILT3 mAb (c52B8) tumor cell survival/growth human immune modulation AML PBMC lines pre-clinical vitro vivo models. Methods ILT3 mRNA surface expression levels were measured by RNAseq FACS, respectively. from patients different treated c52B8 vitro.A systemic model was generated IV inoculation NSG mice luciferase-transfected MV-4-11 or without engraftment. Tumor bearing weekly c52B8, modified to contain Fc either IgG1 IgG4 subclass. growth bioluminescence imaging (BLI).CyTOF performed phenotype culture bone marrow samples after treatment.THP-1 cells/human T co-cultures stimulated anti-CD3/CD28 antibodies c52B8. Human activity assessed IFNγ production using MSD ELISA. Results In high patient PBMC, treatment decreased frequency blasts, modulated Tregs, increased cells. model, significantly reduced burden vivo, regardless IgG Importantly, inhibition occurred absence PBMC. Additional post-mortem CyTOF analysis cells MV-4-11/human inoculated confirmed reduction identified CD3-CD19- following treatment. THP-1/human co-cultures, reversed THP-1 induced suppression, as enhanced production. Conclusions Anti-ILT3 efficacious blocking progression directly influencing enhancing These studies support potential role for this compound humans. Ethics Approval All animal work reviewed approved Merck IACUC before experiments conducted.