Background/Aims: Adult T-cell leukemia/lymphoma (ATL) is a very aggressive T cell malignancy that carries a poor prognosis, primarily due to its resistance to chemotherapy and to life-threatening infectious complications. Interferon-alpha (IFNa) has been used in combination with the anti-retroviral drug zidovudine to treat patients with ATL. However, the efficacy of long-term therapy is significantly limited due to the systemic toxicity of IFNa. Methods: We utilized phage display library screening to identify short peptides that specifically bind to Jurkat T lymphocyte leukemia cells. By fusing the Jurkat-binding peptide to the C-terminus of IFNa, we constructed an engineered chimeric IFNa molecule (IFNP) for the treatment of ATL. Results: We found that IFNP exhibited significantly higher activity than wild type IFNa in inhibiting the growth of leukemia cells and inducing cell blockage at the G0/G1 phase. The synthetic IFNP molecule exerted its antitumor activity by upregulating the downstream genes involved in the STAT1 pathway and in apoptosis. Using a cell receptor binding assay, we showed that this Jurkat-binding peptide facilitated the binding affinity of IFNa to the cell surface type I IFN receptor. Conclusion: The isolated Jurkat-binding peptide significantly potentiates the therapeutic activity of IFNa in T lymphocyte leukemia cells. The engineered IFNP molecule may prove to a novel antitumor approach in the treatment of patients with ATL. (C) 2017 The Author(s) Published by S. Karger AG, Basel
[1]Jilin Univ, Hosp 1, Stem Cell & Canc Ctr, Changchun, Peoples R China.
[2]Stanford Univ, Sch Med, Palo Alto Vet Inst Res, Palo Alto, CA 94304 USA.
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