Abstract
Previously, we found that dysfunctional natural killer (NK) cells with low interferon gamma (IFN-γ) 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-γ 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-γ levels were expressed in AML-mononuclear cells exposed to P4. Additionally, T and NK cell levels were restored, as were high IFN-γ 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.
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This work was financially supported by a grant from the National Research Foundation (NRF, 2018R1D1A1A09083557), Ministry of Education, Republic of Korea.
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JY Lee, S Park, AR Han, and HS Hwang performed the experiments and analyzed the data. JY Lee and HJ Kim wrote the manuscripts.
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All experiments were performed with authorization from the Institutional Review Board for Human Research at the Catholic University of Korea (KC19TESI0462). The patients/participants provided their written informed consent to participate in this study. All protocols for testing the animals were approved by the Catholic University of Korea's Institutional Animal Care and Use Committee (CUMC-2019-0135-01).
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Lee, J.Y., Park, S., Han, AR. et al. Therapeutic potential of FLT4-targeting peptide in acute myeloid leukemia. Cancer Immunol Immunother 72, 2919–2925 (2023). https://doi.org/10.1007/s00262-023-03385-8
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DOI: https://doi.org/10.1007/s00262-023-03385-8