Phase I Study of Multiple Epitope Peptide Vaccination in Patients With Recurrent or Persistent Cervical Cancer

Kosei Hasegawa, Yuji Ikeda, Yuko Kunugi, Akira Kurosaki, Yuichi Imai, Shunsuke Kohyama, Shoji Nagao, Eito Kozawa, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Keiichi Fujiwara

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Cancer immunotherapy has now been established as a leading standard therapeutic option in a subset of patients with cancer. In this study, we conducted a phase I dose-escalation trial using a mixture of 5 peptides to vaccinate cervical cancer patients with HLAA 2402. The primary endpoints were safety and determination of a recommended vaccine dose, and the secondary endpoints were evaluations of immunologic responses and clinical efficacy. All patients had recurrent or persistent disease and had failed to respond to or were intolerant to prior standard chemotherapy. Peptides derived from forkhead box protein M1 (FOXM1), maternal embryonic leucine zipper kinase (MELK), Holliday junction-recognition protein, and vascular endothelial growth factor receptors 1 and 2 were administered to 9 patients in a 3 patient-cohort design, with doses of 0.5, 1, or 2mg of each of the individual peptides in a mixture with incomplete Freunds adjuvant. The major adverse events were anemia and injection site reactions, which were seen in 77.8% (7/9) and 66.7% (6/9) of patients, respectively. Grade 3 anemia was observed in 1 patient. No dose-limiting toxicity of the vaccine was observed. Seven (78%) patients achieved stable disease, and the median progression-free survival was 3.3 months (102 d). Interferon-? enzyme-linked immunospot assays for each of the 5 antigens showed that 8 (89%) and 7 (78%) patients had high T-cell responses to FOXM1 and MELK, respectively. In conclusion, we demonstrated that this 5-peptide vaccine was tolerable, and that FOXM1 andMELK could be promising targets for immunotherapy in patients with cervical cancer.

Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalJournal of Immunotherapy
Volume41
Issue number4
DOIs
Publication statusPublished - 2018
Externally publishedYes

Keywords

  • Cervical cancer
  • Immunotherapy
  • Peptide
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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