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WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objective

The aim of the present study was to analyze the long-term survival effects of WT1 peptide vaccine, in addition to its anti-tumor effects and toxicity.

Methods

A phase II clinical trial was conducted during the period of 2004–2010 at Osaka University Hospital, Osaka, Japan. The patients who had gynecologic malignancies progressing against previous treatments received WT1 peptide vaccine intradermally at 1-week intervals for 12 weeks. The vaccination was allowed to further continue, unless the patient’s condition became significantly worse due to the disease progression.

Results

Forty out of 42 patients, who met all the inclusion criteria, underwent WT1 peptide vaccine. Among these 40 patients, stable disease was observed in 16 cases (40 %). Skin toxicity of a grade 1, 2 and 3 occurred in 25 cases (63 %), 9 cases (23 %) and a single case (3 %), respectively, and liver toxicity of grade 1 in a single case (3 %). The overall survival period was significantly longer in cases positive for the WT1 peptide-specific delayed-type hypersensitivity (DTH) reaction after the vaccination, compared to those negative for the DTH reaction (p = 0.023). Multivariate Cox proportional hazards analysis demonstrated that the adjusted hazard ratio for the negative DTH reaction was 2.73 (95 % CI 1.04–7.19, p = 0.043).

Conclusion

WT1 peptide vaccine may be a potential treatment, with limited toxicity, for gynecologic malignancies that have become resistant to conventional therapies. Larger scale of clinical studies is required to establish the efficacy of the WT1 peptide vaccine for gynecologic malignancies.

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Abbreviations

CR:

Complete response

CT:

Computed tomography

HLA:

Human leukocyte antigen

HPV:

Human papillomavirus

OS:

Overall survival

PD:

Progressive disease

PFS:

Progression-free survival

PR:

Partial response

PS:

Performance status

RECIST:

Response evaluation criteria in solid tumor

RR:

Responsive rate

SD:

Stable disease

TC:

Paclitaxel and carboplatin

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Acknowledgments

We would like to thank Dr. G.S. Buzard, US CDCP, for his editing of our manuscript. We are also grateful to Ms. T. Umeda for her excellent technical assistance.

Conflict of interest

The authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Takashi Miyatake, Yutaka Ueda, Akiko Morimoto, Takayuki Enomoto & Tadashi Kimura

  2. Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Sumiyuki Nishida, Akihiro Tsuboi & Yusuke Oji

  3. Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yoshihiro Oka

  4. Department of Biomedical Informatics, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toshiaki Shirakata

  5. Department of Immunopathology WPI Immunology Frontier Research Center, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yoshihiro Oka

  6. Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Naoki Hosen

  7. Department of Pathology, Kansai Rosai Hospital, 69-1-3 Inabasou, Amagasaki, Hyogo, 660-8511, Japan

    Shin-ichi Nakatsuka

  8. Department of Clinical Statistics, Yokohama City University Medical Center, 4-57, Minami-ku Urabune-cho, Yokohama, Kanagawa, 232-0024, Japan

    Satoshi Morita

  9. Department of Health and Community Medicine, Nagoya University Graduate School of Medicine, 65, Showa-ku Tsurumai-cho, Nagoya, Aichi, 466-8550, Japan

    Junichi Sakamoto

  10. Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Haruo Sugiyama

Authors
  1. Takashi Miyatake
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  2. Yutaka Ueda
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  3. Akiko Morimoto
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  4. Takayuki Enomoto
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  5. Sumiyuki Nishida
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  6. Toshiaki Shirakata
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  7. Yoshihiro Oka
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  8. Akihiro Tsuboi
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  9. Yusuke Oji
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  10. Naoki Hosen
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  11. Shin-ichi Nakatsuka
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  12. Satoshi Morita
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  13. Junichi Sakamoto
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  14. Haruo Sugiyama
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  15. Tadashi Kimura
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Corresponding author

Correspondence to Yutaka Ueda.

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Miyatake, T., Ueda, Y., Morimoto, A. et al. WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial. J Cancer Res Clin Oncol 139, 457–463 (2013). https://doi.org/10.1007/s00432-012-1348-2

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  • DOI: https://doi.org/10.1007/s00432-012-1348-2

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