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N/A
30 Years
80 Years
Open (Enrolling)
Both
Carcinoma, Hepatocellular

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Trial Information


Hepatoma ranks the first two of the cancer mortality list in Taiwan, and there are currently
no effective treatment options for advanced HCC. Therefore, novel medical intervention is
needed to improve the survival and quality of life of these patients. Dendritic cells are
the most potent type of antigen presenting cells in the human body, and are involved in the
regulation of both innate and adoptive immune responses. It is assumed that matured antigen
presenting cells pulsed in vitro with appropriate tumor associated antigens under optimal
activation conditions might generate or activate a cytotoxic T lymphocyte response against
tumor cells and thereby inhibit tumor growth(1,2).

Although there are exciting results of tumor vaccine in animal models but successful
clinical tries are lacking. There are some problems needed to be resolved such as immune
deficiency of the cancer patients, defect of T cell receptors or the immune evasion of
tumor. The efficacy of tumor vaccine is mainly affected by both the heterogenicity of tumor
cells and complexity of tumor antigens. Tumor lysates which include multiple antigens, are
supposed to be a good source of tumor antigens(3-7). The purpose of this study is to
investigate the ability of autologous peripheral blood monocyte-derived dendritic cells
(DCs) from hepatoma patients pulsed with autologous tumor lysate to elicit T cells
cytotoxicity against hepatoma cells ex vivo. We plan to do HCC primary culture and DCs are
derived from peripheral blood monocytes by triggering differentiation with recombinant human
granulocyte macrophage colony stimulating factor (rhGM-CSF) and interleukin-4 (rhIL-4) to
immature DCs. Immature DCs will be pulsed with autologous hepatoma cell lysates and matured
by using a cytokine cocktail. Surface molecule expression on DCs will be analysed by flow
cytometry. The ability of the pulsed DCs to stimulate autologous T cell proliferation will
be assessed by using carboxyfluorescein diacetate, succinimidyl ester (CFSE) staining. The
cytotoxicity of DC-stimulated T cells against primarily cultured hepatoma cells will be
estimated by using trypan blue exclusion test. The purpose is to investigate the ability of
autologous peripheral blood monocyte-derived dendritic cells (DCs) from hepatoma patients
pulsed with autologous tumor lysate to elicit T cells cytotoxicity against hepatoma cells ex
vivo.

Reference

1. Liu KJ, Wang CC, Chen LT, Cheng AL, Lin DT, Wu YC, Yu WL, Hung YM, Yang HY, Juang SH,
Whang-Peng J. Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in
HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with
dendritic cells loaded with CEA peptides. Clin Cancer Res. 2004 Apr 15;10(8):2645-51.
PMID: 15102666

2. Chan RC, Pang XW, Wang YD, Chen WF, Xie Y. Transduction of dendritic cells with
recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to
target hepatoma cells. Br J Cancer. 2004 Apr 19;90(8):1636-43. PMID: 15083197

3. Iwashita Y, Tahara K, Goto S, Sasaki A, Kai S, Seike M, Chen CL, Kawano K, Kitano S. A
phase I study of autologous dendritic cell-based immunotherapy for patients with
unresectable primary liver cancer. Cancer Immunol Immunother. 2003 Mar;52(3):155-61.
Epub 2003 Feb 06. PMID: 12649744

4. Ladhams A, Schmidt C, Sing G, Butterworth L, Fielding G, Tesar P, Strong R, Leggett B,
Powell L, Maddern G, Ellem K, Cooksley G. Treatment of non-resectable hepatocellular
carcinoma with autologous tumor-pulsed dendritic cells. J Gastroenterol Hepatol. 2002
Aug;17(8):889-96. PMID: 12164965

5. Parajuli P, Sloan AE. Dendritic cell-based immunotherapy of malignant gliomas. Cancer
Invest. 2004;22(3):405-16. PMID: 15493362

6. Song SY, Kim HS. Strategies to improve dendritic cell-based immunotherapy against
cancer. Yonsei Med J. 2004 Jun 30;45 Suppl:48-52. PMID: 15250050

7. Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping
the way. Nat Med. 2004 May;10(5):475-80. PMID: 15122249


Inclusion Criteria:



- Hepatoma patients indicated for operation

Exclusion Criteria:

- With major systemic disease including other cancer or coagulopathy

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Ching-Chung Lin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Division of Gastroenterology, Mackay Memorial Hospital

Authority:

Taiwan: Department of Health

Study ID:

MMH-I-S-166

NCT ID:

NCT00327496

Start Date:

June 2005

Completion Date:

June 2006

Related Keywords:

  • Carcinoma, Hepatocellular
  • Carcinoma
  • Carcinoma, Hepatocellular

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