Immunogenicity and toxicity of transferrin receptor-targeted hybrid peptide as a potent anticancer agent
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Transferrin receptor (TfR) is a cell membrane-associated glycoprotein involved in the cellular uptake of iron and the regulation of cell growth. Recent studies have shown elevated expression levels of TfR on cancer cells compared with normal cells. We previously designed a TfR-lytic hybrid peptide, which combines the TfR-binding peptide and a lytic peptide, and reported that it bound specifically to TfR and selectively killed cancer cells. Furthermore, the intravenous administration of TfR-lytic peptide in an athymic mouse model significantly inhibited tumor progression. To evaluate the immunogenicity of this peptide as a novel and potent anticancer agent, we investigated whether TfR-lytic hybrid peptide elicits cellular and humoral immune responses to produce antibodies. We also examined the toxicity of this peptide in syngeneic mice.
We performed hematologic and blood chemistry test and histological analysis and assessed hemolytic activity to check toxicity. To evaluate the immunogenicity, measurement of murine interferon-gamma and detection of TfR-lytic-specific antibody by ELISA were demonstrated.
No T cell immune response or antibodies were detected in the group treated with TfR-lytic hybrid peptide. No hematologic toxicity, except for a decrease in leukocytes, was observed, and no remarkable influence on metabolic parameters and organs (liver, kidney, and spleen) was noted.
Therefore, TfR-lytic hybrid peptide might provide an alternative therapeutic option for patients with cancer.
KeywordsTransferrin receptor Immunogenicity Toxicity Peptide drug Molecular target drug for cancer treatment Immunotoxin
- 5.Foss FM (2000) DAB (389) IL-2 (ONTAK): a novel fusion toxin therapy for lymphoma. Clin Lymphoma 2:110–117Google Scholar
- 6.Piascik P (1999) FDA approves fusion protein for treatment of lymphoma. J Am Pharm Assoc 39:571–572Google Scholar
- 21.Fuessel S, Meye A, Schmitz M, Zastrow S, Linné C, Richter K, Löbel B, Hakenberg OW, Hoelig K, Rieber EP, Wirth MP (2006) Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. Prostate 66:811–821PubMedCrossRefGoogle Scholar
- 26.Chirasani SR, Markovic DS, Synowitz M, Eichler SA, Wisniewski P, Kaminska B, Otto A, Wanker E, Schäfer M, Chiarugi P, Meier JC, Kettenmann H, Glass R (2009) Transferrin-receptor-mediated iron accumulation controls proliferation and glutamate release in glioma cells. J Mol Med (Berl) 87:153–167CrossRefGoogle Scholar