Journal of Gastrointestinal Surgery

, Volume 17, Issue 9, pp 1609–1617

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

  • Masanori Kobayashi
  • Tomoyo Sakabe
  • Hirofumi Abe
  • Mitsugu Tanii
  • Hidenori Takahashi
  • Asako Chiba
  • Eri Yanagida
  • Yuta Shibamoto
  • Masahiro Ogasawara
  • Shun-ichi Tsujitani
  • Shigeo Koido
  • Kazuhiro Nagai
  • Shigetaka Shimodaira
  • Masato Okamoto
  • Yoshikazu Yonemitsu
  • Noboru Suzuki
  • Masaki Nagaya
  • The DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT)
Original Article

DOI: 10.1007/s11605-013-2286-2

Cite this article as:
Kobayashi, M., Sakabe, T., Abe, H. et al. J Gastrointest Surg (2013) 17: 1609. doi:10.1007/s11605-013-2286-2

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.

Keywords

Dendritic cellWT1MUC1Immunotherapy and biliary tract cancer

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

Supplementary material

11605_2013_2286_MOESM1_ESM.doc (56 kb)
ESM 1(DOC 55 kb)

Copyright information

© The Society for Surgery of the Alimentary Tract 2013

Authors and Affiliations

  • Masanori Kobayashi
    • 1
    • 5
  • Tomoyo Sakabe
    • 1
  • Hirofumi Abe
    • 2
  • Mitsugu Tanii
    • 3
  • Hidenori Takahashi
    • 3
  • Asako Chiba
    • 4
  • Eri Yanagida
    • 4
  • Yuta Shibamoto
    • 5
  • Masahiro Ogasawara
    • 6
  • Shun-ichi Tsujitani
    • 7
  • Shigeo Koido
    • 8
  • Kazuhiro Nagai
    • 9
  • Shigetaka Shimodaira
    • 10
  • Masato Okamoto
    • 11
  • Yoshikazu Yonemitsu
    • 12
  • Noboru Suzuki
    • 13
  • Masaki Nagaya
    • 4
    • 13
  • The DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT)
  1. 1.Seren Clinic NagoyaIsokaiNagoyaJapan
  2. 2.Seren Clinic KobeIsokaiKobeJapan
  3. 3.Seren Clinic FukuokaIsokaiFukuokaJapan
  4. 4.Seren Clinic TokyoIsokaiTokyoJapan
  5. 5.Department of RadiologyNagoya City University Graduate School of Medical SciencesNagoyaJapan
  6. 6.Department of HematologySapporo Hokuyu HospitalSapporoJapan
  7. 7.National Center for Grobal Health and MedicineTokyoJapan
  8. 8.Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineKashiwaJapan
  9. 9.Transfusion and Cell Therapy UnitNagasaki University HospitalNagasakiJapan
  10. 10.Cell Processing CenterShinshu University HospitalMatsumotoJapan
  11. 11.Institute for Advanced Medical ResearchKeio University School of MedicineTokyoJapan
  12. 12.R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  13. 13.Department of ImmunologySt. Marianna University School of MedicineKawasakiJapan