Cytotoxicity Induced by Tumor Lysate Pulsed Dendritic Cells Against Autologous Hepatocellular Carcinoma Cells

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2005 by Mackay Memorial Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Mackay Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00327496
First received: May 16, 2006
Last updated: NA
Last verified: June 2005
History: No changes posted
  Purpose

Hepatoma ranks the first on the cancer mortality list in Taiwan, and there are currently no other effective treatment options for advanced HCC. Therefore, alternative 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. If we use matured antigen presenting cells pulsed in vitro with appropriate tumor associated antigens under optimal activation conditions. It is anticipated that such treatment might generate or reactivate a cytotoxic T lymphocyte response against tumor cells and thereby inhibit tumor growth.

Although there are excited results of tumor vaccine in animal models but successful clinical tries are rare. There are still some problems needed to be resolved such as immune deficiency of the cancer patients or the defect of T cell receptors or the problems of tumor escape. There are complex compositions in tumor cells to be a tumor antigen that will influence the efficacy of tumor vaccine, so we are going to use tumor lysate to be a tumor antigen.

In this study, the generation of dendritic cells from the patient’s peripheral blood will use rhGM-CSF and rhIL-4 as stimulating factors, and matured dendritic cells will pulse with tumor lysate, the ex vivo T cell cytotoxicity for the primary tumor cell will be test. We hope to cooperate with basic study group in our hospital to do more ex vivo tests and clinical trials in the future.


Condition Intervention
Carcinoma, Hepatocellular
Biological: DC vaccine

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

Resource links provided by NLM:


Further study details as provided by Mackay Memorial Hospital:

Estimated Enrollment: 10
Study Start Date: June 2005
Estimated Study Completion Date: June 2006
Detailed Description:

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
  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hepatoma patients indicated for operation

Exclusion Criteria:

  • With major systemic disease including other cancer or coagulopathy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00327496

Sponsors and Collaborators
Mackay Memorial Hospital
Investigators
Principal Investigator: Ching-Chung Lin, MD Division of Gastroenterology, Mackay Memorial Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00327496     History of Changes
Other Study ID Numbers: MMH-I-S-166
Study First Received: May 16, 2006
Last Updated: May 16, 2006
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 30, 2014