Top

Journal of Hepato-Biliary-Pancreatic Sciences

Published in:

01-03-2012 | Original article

Clinical utilization of postoperative dendritic cell vaccine plus activated T-cell transfer in patients with intrahepatic cholangiocarcinoma

Authors: Koichi Shimizu, Yoshihito Kotera, Atsushi Aruga, Nobuhiro Takeshita, Ken Takasaki, Masakazu Yamamoto

Published in: Journal of Hepato-Biliary-Pancreatic Sciences | Issue 2/2012

Abstract

Background

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is extremely poor and the recurrence rate after curative operation is very high. There is no standard treatment to prevent recurrence of ICC. In this study, we investigated the clinical utilization of a dendritic cell vaccine plus activated T-cell transfer in an adjuvant setting for postoperative ICC.

Methods

36 patients with ICC were vaccinated at least 3 times with autologous tumor lysate pulsed dendritic cells plus ex-vivo activated T-cell transfer. The 5-year progression-free survival (PFS) and overall survival (OS) were measured and compared with those of 26 patients who received the curative operation alone as a concurrent control. The registration number was UMIN000005820.

Results

The median PFS and OS were 18.3 and 31.9 months in the patients receiving adjuvant immunotherapy and 7.7 and 17.4 months in the group receiving surgery alone (p = 0.005 and 0.022, respectively). In the treated group, patients whose skin reactions were 3 cm or more at the vaccine site showed dramatically better prognosis (PFS p < 0.001, OS p = 0.001).

Conclusions

A postoperative dendritic cell vaccine plus activated T-cell transfer would be a feasible and effective treatment for preventing recurrence and achieving long-term survival in ICC patients.

Yamamoto M, Ariizumi S. Intrahepatic recurrence after surgery in patients with intrahepatic cholangiocarcinoma. J Gastoenterol. 2006;41(9):925–6.CrossRef

Yamamoto M, Takasaki K, Otsubo T, Katsuragawa H, Katagiri S. Recurrence after surgical resection of intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg. 2001;8(2):154–7.PubMedCrossRef

Kotera Y, Shimizu K, Mule JJ. Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res. 2001;61(22):8105–9.PubMed

Shimizu K, Thomas EK, Giedlin M, Mule JJ. Enhancement of tumor-lysate- and peptide-pulsed dendritic cell-based vaccines by the addition of foreign helper protein. Cancer Res. 2001;61(6):2618–24.PubMed

Engell-Noerregaard L, Hansen TH, Andersen MH, Straten PT, Svane IM. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters. Cancer Immunol Immunother. 2009;58(1):1–14.PubMedCrossRef

Shimizu K, Tanigawa K, Takeshita N, Fujisawa T, Takasaki K, Yamamoto M, Aruga A. A Phase I/II trial of combination therapy of tumor lysate-pulsed dendritic cells and adoptive transfer of anti-CD3 activated T cells (ATVAC) in patients with advanced gastrointestinal (GI) cancers. J Immunother. 2008;31(9):926.

De Vleeschouwer S, Fieuws S, Rutkowski S, Van Calenbergh F, Van Loon J, Goffin J, Sciot R, Wilms G, Demaerel P, Warmuth-Metz M, Soerensen N, Wolf JEA, Wagner S, Kaempgen E, Van Gool SW. Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme. Clin Cancer Res. 2008;14(10):3098–104.PubMedCrossRef

Rutlowski S, De Vleeschouwer S, Kaempgen E, Wolf JEA, Kuhl J, Demaerel P, Warmuth-Metz M, Flamen P, Van Calenbergh F, Plets C, Sorensen N, Opitz A, Van Gool SW. Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study. Br J Cancer. 2004;91(9):1656–62.

Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, Shimada K, Sakamoto M, Hirohashi S, Ohashi Y, Kakizoe T. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomized trial. Lancet. 2000;356(9232):802–7.PubMedCrossRef

10.

Chang AE, Aruga A, Cameron MJ, Sondak VK, Normolle DP, Fox BA, Shu S. Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2. J Clin Oncol. 1997;15(2):796–807.PubMed

11.

Matsuda A, Kuno A, Kawamoto T, Matsuzaki H, Irimura T, Ikehara Y, Zen Y, Nakanuma Y, Yamamoto M, Ohkohchi N, Shoda J, Hirabayashi J, Narimatsu H. Wisteria floribunda agglutinin-positive mucin 1 is a sensitive biliary marker for human cholangiocarcinoma. Hepatology. 2010;52(1):174–82.PubMedCrossRef

12.

Matsumura N, Yamamoto M, Aruga A, Takasaki K, Nakano M. Correlation between expression of MUC1 core protein and outcome after surgery in mass-forming intrahepatic cholangiocarcinoma. Cancer. 2001;94(6):1770–6.CrossRef

13.

Lepisto AJ, Moser AJ, Zeh H, Lee K, Bartlett D, McKolanis JR, Geller BA, Schmotzer A, Potter DP, Whiteside T, Finn OJ, Ramanathan RK. A phase I/II study of a MUC1 peptide pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors. Cancer Ther. 2008;6(B):955–64.PubMed

14.

Higuchi R, Yamamoto M, Hatori T, Hatori T, Shimizu K, Imai K, Takasaki K. Intrahepatic cholangiocarcinoma with lymph node metastasis successfully treated by immunotherapy with CD3-activated T cells and dendritic cells after surgery: report of a case. Surg Today. 2006;36(6):559–62.PubMedCrossRef

15.

Miyazawa M, Ohsawa R, Tsunoda T, Hirono S, Kawai M, Tani M, Nakamura Y, Yamaue H. Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci. 2010;101(2):422–9.CrossRef

16.

Koike N, Pilon-Thomas S, Mule JJ. Nonmyeloablative chemotherapy followed by T-cell adoptive transfer and dendritic cell-based vaccination results in rejection of established melanoma. J Immunother. 2008;31(4):402–12.PubMedCrossRef

17.

Matsushita N, Pilon-Thomas SA, Martin LM, Riker AI. Comparative methodologies of regulatory T cell depletion in a murine melanoma model. J Immunol Methods. 2008;333(1–2):167–79.PubMedCrossRef

18.

Morse MA, Hobeika AC, Osada T, Serra D, Niedzwiechi D, Lyerly DH, Clay TM. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood. 2008;112(3):610–8.PubMedCrossRef

19.

Fukuma D, Matsuyoshi H, Hirta S, Kurisaki A, Motomura Y, Yoshitake Y, Shinohara M, Nishimura Y, Senju S. Cancer prevention with semi-allogeneic ES cell-derived dendritic cells. Biochem Biophys Res Commun. 2005;335(1):5–13.PubMedCrossRef

Title: Clinical utilization of postoperative dendritic cell vaccine plus activated T-cell transfer in patients with intrahepatic cholangiocarcinoma
Authors: Koichi Shimizu
Yoshihito Kotera
Atsushi Aruga
Nobuhiro Takeshita
Ken Takasaki
Masakazu Yamamoto
Publication date: 01-03-2012
Publisher: Springer Japan
Published in: Journal of Hepato-Biliary-Pancreatic Sciences / Issue 2/2012
Print ISSN: 1868-6974
Electronic ISSN: 1868-6982
DOI: https://doi.org/10.1007/s00534-011-0437-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical utilization of postoperative dendritic cell vaccine plus activated T-cell transfer in patients with intrahepatic cholangiocarcinoma

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2012

A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer

Diagnostic ability of MDCT to assess right hepatic artery invasion by perihilar cholangiocarcinoma with left-sided predominance

Pancreaticoduodenectomy for invasive pancreatic cancer (with video)

Portal vein resection in pancreaticoduodenectomy (with video)

Pancreatic dissection in the procedure of pancreaticoduodenectomy (with videos)

Pancreaticojejunostomy without stent (with video)