Carcinoma, HepatocellularNCT00327496
Cytotoxicity Induced by Tumor Lysate Pulsed Dendritic Cells Against Autologous Hepatocellular Carcinoma Cells
A study testing DC vaccine in people with Carcinoma, Hepatocellular, run by Mackay Memorial Hospital.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- DC vaccine
- Type of treatment
- Vaccines
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Jun 2005to Jun 2006
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hepatoma patients indicated for operation
Who cannot join
- With major systemic disease including other cancer or coagulopathy
About this study
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.
Read the 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
- 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
- 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
- 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
- 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
- Parajuli P, Sloan AE. Dendritic cell-based immunotherapy of malignant gliomas. Cancer Invest. 2004;22(3):405-16. PMID: 15493362
- 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
- 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
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- DC vaccine
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DC vaccineBiological
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2006 (estimated)
- Study startJun 2005
- Study completionJun 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants
Sponsor and investigators
- Lead sponsor
- Mackay Memorial Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Ching-Chung Lin, MD, Principal investigator, Division of Gastroenterology, Mackay Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00327496
- Sponsor's protocol ID
- MMH-I-S-166
- Status last verified
- Jun 2005
- First submitted
- 16 May 2006
- Last updated
- 18 May 2006
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cytotoxicity Induced by Tumor Lysate Pulsed Dendritic Cells Against Autologous Hepatocellular Carcinoma Cells
- ClinicalTrials.gov ID
- NCT00327496
- Acronym / sponsor ID
- MMH-I-S-166
- Conditions
- Carcinoma, Hepatocellular
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants
- Lead sponsor
- Mackay Memorial HospitalUniversity, hospital or other
- Study start
- Jun 2005
- Study completion
- Jun 2006
- First posted
- 18 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- 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
- 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
- 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
- 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
- Parajuli P, Sloan AE. Dendritic cell-based immunotherapy of malignant gliomas. Cancer Invest. 2004;22(3):405-16. PMID: 15493362
- 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
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Hepatoma patients indicated for operation
Key exclusion criteria (1 listed)
- With major systemic disease including other cancer or coagulopathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DC vaccine | Biological | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2006.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ching-Chung Lin, MD principal investigator
Division of Gastroenterology, Mackay Memorial Hospital
Questions about this trial
What is this clinical trial studying?
A study testing DC vaccine in people with Carcinoma, Hepatocellular, run by Mackay Memorial Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 May 2006. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2006.