Therapeutic potential of FLT4-targeting peptide in acute myeloid leukemia

Previously, we found that dysfunctional natural killer (NK) cells with low interferon gamma (IFN-gamma) were restored in acute myeloid leukemia (AML) by the FLT4 antagonist MAZ51. Here, we developed 12 peptides targeting FLT4 for clinical application and examined whether they restored the frequency of lymphocytes, especially T cells and NK cells, and high IFN-gamma expression, as MAZ51 treatment did in our previous study. Although clinical data from using peptides are currently available, peptides targeting FLT4 to modulate immune cells have not been fully elucidated. In this study, we focus on novel peptide 4 (P4) from the intracellular domain of FLT4 because it had dominant negative activity. Similar to MAZ51, high IFN-gamma levels were expressed in AML-mononuclear cells exposed to P4. Additionally, T and NK cell levels were restored, as were high IFN-gamma levels, in a leukemic environment when P4 was treated. Interestingly, the regulatory T cells were significantly decreased by P4, implying the role of peptide in tumor niche. Overall, we demonstrated the therapeutic value of functionally modulating lymphocytes using a peptide targeting FLT4 and proposed the development of advanced therapeutic approaches against AML by using immune cells.

Automated summary

In this study, we developed 12 peptides targeting FLT4 for clinical application and found that peptide 4 (P4) restored the functionality of dysfunctional NK cells and T cells in patients with AML. P4 treatment also increased the expression of IFN-gamma and decreased the number of regulatory T cells. Overall, we demonstrated the therapeutic potential of modulating lymphocytes using FLT4-targeting peptides for advanced approaches against AML.