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Dendritic Cell-Based Immunotherapy Targeting Synthesized Peptides for Advanced Biliary Tract Cancer

  • Original Article
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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

The aim of this retrospective study was to clarify the safety and efficacy of dendritic cell (DC)-based immunotherapy targeting synthesized peptides, Wilms tumor 1 (WT1) and Mucin 1, cell surface associated (MUC1) for biliary tract cancers (BTCs).

Methods

Sixty-five patients who had nonresectable, recurrent, or metastatic BTCs and received the DC-based immunotherapy were selected for the study. DCs were pulsed with WT1 and/or MUC1. The adverse events (AEs) and clinical responses were examined.

Results

No serious treatment-related AEs were observed. Median survival time (MST) from diagnosis and from the first vaccination was 18.5 and 7.2 months, respectively. By multivariate Cox proportional hazard analysis, the significant independent factors were found to be (1) combined chemotherapy, (2) albumin level ≥4.0 g/dL before vaccination, (3) C-reactive protein level <0.5 mg/dL before vaccination, and (4) fever after vaccination. The MST from the first vaccination with or without chemotherapy was 8.2 and 5.3 months, respectively (P = 0.016), and MST for the patients with prognostic nutritional index ≥40 and <40 was 8.1 and 5.0 months, respectively (P = 0.023).

Conclusions

Although a small uncontrolled nonrandomized study, DC-based immunotherapy for BTCs was safe and produced a clinical response for the patients who underwent chemotherapy and maintained a good nutrition status.

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Abbreviations

BTC:

Biliary tract cancer

DC:

Dendritic cell

WT1:

Wilms tumor 1

MUC1:

Mucin 1, cell surface associated

IHC staining:

Immunohistochemical staining

MST:

Median survival time

ORR:

Objective response rate

DCR:

Disease control rate

RECIST:

Response Evaluation Criteria in Solid Tumors

mGPS:

Modified Glasgow prognostic score

PNI:

Prognostic nutritional index

CRP:

C-reactive protein

Treg:

Regulatory T cell

CTLs:

Cytotoxic T lymphocytes

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Acknowledgments

This report is dedicated to the patients who participated in our study and their primary oncology doctors. No funding supported this study.

Conflict of Interest

The authors have no financial or personal relationships with other people or organizations that could inappropriately influence our work.

Author information

Authors and Affiliations

  1. Seren Clinic Nagoya, Isokai, 4-14-2 Sakae, Naka-ku, Nagoya, 460-0008, Japan

    Masanori Kobayashi & Tomoyo Sakabe

  2. Seren Clinic Kobe, Isokai, 4-4-17 Kanou-cho, Chuo-ku, Kobe, 650-0001, Japan

    Hirofumi Abe

  3. Seren Clinic Fukuoka, Isokai, 1-2-12 Tenjin, Chuo-ku, Fukuoka, Fukuoka, 810-0001, Japan

    Mitsugu Tanii & Hidenori Takahashi

  4. Seren Clinic Tokyo, Isokai, 2-10-2 Shirokanedai, Minato-ku, Tokyo, 108-0071, Japan

    Asako Chiba, Eri Yanagida & Masaki Nagaya

  5. Department of Radiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Masanori Kobayashi & Yuta Shibamoto

  6. Department of Hematology, Sapporo Hokuyu Hospital, 6-5-1 Higashi-Sapporo 6-jyou Shiroishi-ku, Sapporo, Hokkaido, 003-0006, Japan

    Masahiro Ogasawara

  7. National Center for Grobal Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan

    Shun-ichi Tsujitani

  8. Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Shigeo Koido

  9. Transfusion and Cell Therapy Unit, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Kazuhiro Nagai

  10. Cell Processing Center, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Shigetaka Shimodaira

  11. Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi Shinjuku, Tokyo, 160-8582, Japan

    Masato Okamoto

  12. R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Yoshikazu Yonemitsu

  13. Department of Immunology, St. Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki, 261-8511, Japan

    Noboru Suzuki & Masaki Nagaya

Authors
  1. Masanori Kobayashi
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  2. Tomoyo Sakabe
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  3. Hirofumi Abe
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  4. Mitsugu Tanii
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  5. Hidenori Takahashi
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  6. Asako Chiba
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  7. Eri Yanagida
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  8. Yuta Shibamoto
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  9. Masahiro Ogasawara
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  10. Shun-ichi Tsujitani
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  11. Shigeo Koido
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  12. Kazuhiro Nagai
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  13. Shigetaka Shimodaira
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  14. Masato Okamoto
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  15. Yoshikazu Yonemitsu
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  16. Noboru Suzuki
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  17. Masaki Nagaya
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Consortia

The DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT)

Corresponding author

Correspondence to Masaki Nagaya.

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Kobayashi, M., Sakabe, T., Abe, H. et al. Dendritic Cell-Based Immunotherapy Targeting Synthesized Peptides for Advanced Biliary Tract Cancer. J Gastrointest Surg 17, 1609–1617 (2013). https://doi.org/10.1007/s11605-013-2286-2

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  • DOI: https://doi.org/10.1007/s11605-013-2286-2

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