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Cancer Immunology, Immunotherapy

, Volume 63, Issue 9, pp 939–946 | Cite as

Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer

  • Moon Jae Chung
  • Jeong Youp Park
  • Seungmin Bang
  • Seung Woo Park
  • Si Young SongEmail author
Original Article

Abstract

Second-line chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer has shown disappointing survival outcomes due to rapid disease progression and performance deterioration. The aim of this phase II trial was to evaluate the efficacy and safety of adoptive immunotherapy using ex vivo-expanded, cytokine-induced killer (CIK) cells in gemcitabine-refractory advanced pancreatic cancer. Patients with advanced pancreatic cancer who showed disease progression during gemcitabine-based chemotherapy were enrolled in this study. For generation of CIK cells, peripheral blood samples were collected from each patient and cultured with anti-CD3 monoclonal antibody and IL-2. Patients received CIK cells intravenously 10 times, every week for 5 weeks and then every other week for 10 weeks. Twenty patients were enrolled between November 2009 and September 2010. The disease control rate was 25 % (4/16 patients). The median progression-free survival (PFS) was 11.0 weeks (95 % CI 8.8–13.2), and the median overall survival (OS) was 26.6 weeks (95 % CI 8.6–44.6). Grade 3 toxicities included general weakness in two patients and thrombocytopenia in one patient. Grade 4 hematologic or non-hematologic toxicity was not observed. Patients showed improvement in pancreatic pain, gastrointestinal distress, jaundice, body image alterations, altered bowel habits, health satisfaction, and sexuality when assessing quality of life (QoL). Adoptive immunotherapy using CIK cells showed comparable PFS and OS to survival data of previous trials that assessed conventional chemotherapies while maintaining tolerability and showing encouraging results in terms of patient QoL in gemcitabine-refractory advanced pancreatic cancer (clinicalTrials.gov number NCT00965718).

Keywords

Adoptive immunotherapy Cytokine-induced killer cells Gemcitabine refractory Pancreatic cancer 

Abbreviations

CIK cells

Cytokine-induced killer cells

CA 19-9

Carbohydrate antigen 19-9

CIs

Confidence intervals

DCR

Disease control rate

ECOG-PS

Eastern Cooperative Oncology Group performance status

EORTC

European Organization for Research and Treatment of Cancer

FACS

Fluorescence-activated cell sorting

HCC

Hepatocellular carcinoma

INR

International normalized ratio

ITT

Intention-to-treat

MHC

Major histocompatibility complex

OFF

Oxaliplatin, folinic acid, and 5-FU

OS

Overall survival

PBMCs

Peripheral blood mononuclear cells

PD

Progressive disease

PFS

Progression-free survival

PP

Per-protocol

QLQ-C30

Quality of Life Questionnaire Core 30

QLQ-PAN26

Quality of Life Questionnaire Core 30 in patients with pancreatic cancer

QoL

Quality of life

SD

Stable disease

VAS

Visual analog scale

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2014_1566_MOESM1_ESM.pdf (713 kb)
Supplementary material 1 (PDF 713 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Moon Jae Chung
    • 1
  • Jeong Youp Park
    • 1
  • Seungmin Bang
    • 1
  • Seung Woo Park
    • 1
  • Si Young Song
    • 1
    Email author
  1. 1.Division of Gastroenterology, Department of Internal MedicineYonsei Institute of GastroenterologySeoulRepublic of Korea

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