Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 3, pp 799–807

Immunogenicity and toxicity of transferrin receptor-targeted hybrid peptide as a potent anticancer agent

  • Megumi Kawamoto
  • Masayuki Kohno
  • Tomohisa Horibe
  • Koji Kawakami
Original Article

DOI: 10.1007/s00280-013-2074-4

Cite this article as:
Kawamoto, M., Kohno, M., Horibe, T. et al. Cancer Chemother Pharmacol (2013) 71: 799. doi:10.1007/s00280-013-2074-4



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.


Transferrin receptorImmunogenicityToxicityPeptide drugMolecular target drug for cancer treatmentImmunotoxin

Supplementary material

280_2013_2074_MOESM1_ESM.ppt (60 kb)
Supplementary Fig. 1 Anti-tumor activity of TfR-lytic hybrid peptide in athymic mouse model in vivo. U251 human glioma cells were implanted subcutaneously into athymic mice. Intravenous injection of either saline (control) or TfR-lytic peptide (3 mg/kg) as indicated by the arrows. Data are expressed as mean ± SD, n = 6 animals in each group. Supplementary material 1 (PPT 60 kb)
280_2013_2074_MOESM2_ESM.ppt (87 kb)
Supplementary Fig. 2 Specific immunoglobulin M for TfR-lytic hybrid peptide or KLH-conjugated TfR-lytic peptide in the serum of treated mice with these peptides. Serum samples were collected on days 12, 19, 26, and 33 in GL261 cells implanting, and (A) used in a serial dilutions, (B) assessed to determine the optical density of serum specimens diluted 1:16. Mean ± SD (n = 3 mice/group). Supplementary material 2 (PPT 87 kb)
280_2013_2074_MOESM3_ESM.doc (41 kb)
Supplementary material 3 (DOC 41 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Megumi Kawamoto
    • 1
  • Masayuki Kohno
    • 1
  • Tomohisa Horibe
    • 1
  • Koji Kawakami
    • 1
  1. 1.Department of Pharmacoepidemiology, Graduate School of Medicine and Public HealthKyoto UniversitySakyo-ku, KyotoJapan