Augmentation of Dendritic Cell-Based Vaccines in Melanoma Patients by Depletion of Regulatory T Cells in Stage IV Melanoma Patients

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-03-31

Study Completion Date

2005-10-31

Brief Summary

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Dendritic cells (DC) are the professional antigen presenting cells of the immune system. Multiple distinct DC lineage's exist and it is now well appreciated that the DC subset and the maturation stage of the DC determines the type of immune response, ranging from a TH1 or TH2 response to immune tolerance. The extremely potent capacity of mature DC to initiate immune responses can be exploited to fight infectious diseases and cancer. Others and we are currently using tumor antigen loaded mature DC in clinical vaccination studies against cancer, and clinical as well as immunological responses have been observed.

Exciting new insights accompany the revival of suppressor T cells, now referred to as regulatory T cells (Treg), and implicate that also Treg play a key role in the control of immunity. Treg constitute a sub-population of CD4+ T cells constitutively expressing the IL-2R alpha-chain (CD25). Treg show remarkably suppressive activities on different components of the immune system, including T lymphocytes and dendritic cells, suggesting they act both at the initiation phase (DC) and at the effector phase (activated T cells) of the immune response. Interestingly, temporal depletion of Treg has been shown to enhance anti-tumor immune responses and in case of prolonged absence of Treg even autoimmunity. Furthermore, data in mouse tumor models indicate that temporal depletion of Treg also results in improved vaccine efficiency in the therapeutic setting, e.g. in mice with a pre-existing tumor. These data imply that in tumor bearing patients depletion of Treg prior to vaccination will improve vaccine efficacy.

In this study we investigate the effect of regulatory T cell (Treg) depletion on the efficacy of DC-based anti-tumor vaccines in a clinical study using melanoma associated antigens tyrosinase and gp100-loaded DC and a depleting anti-CD25 mononuclear antibody (Daclizumab). Our primary objective in this study is the induction of an effective anti-tumor immune response. Our secondary objective is the induction of a clinical response.

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Detailed Description

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Conditions

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Melanoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Daclizumab

Intervention Type DRUG

Dendritic cells

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Histologically documented evidence of melanoma.
2. Stage IV melanoma according to the 2001 AJCC criteria. \[53\] Limited tumor burden; LDH \< 2x upper limit of normal.
3. HLA-A2.1 phenotype according to lymphocyte HLA typing.
4. Expression of gp100 and/or tyrosinase on melanoma cells, as detected by immunohistochemistry, preferably on metastatic tumor, but if not available on primary tumor.
5. ECOG performance status 0-1, life expectancy \> 3 months.
6. Age 18-75 years. -
7. Written informed consent.
8. Expected adequacy of follow-up.
9. WBC \> 3.0 x 109/l, lymphocytes \> 0.8 x 109/l, platelets \> 100 x 109/l, serum creatinine \< 150 μmol/l, serum bilirubin \< 25 μmol/l.

Exclusion Criteria

10. No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases CT scan of the brain should be performed to exclude this.
11. No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.
12. No previous treatment with monoclonal antibodies.
13. No concomitant use of corticosteroids or other immunosuppressive agents.
14. No history of second malignancy within the last 5 years. Adequately treated basal carcinoma of skin or carcinoma in situ of cervix is acceptable within this period.
15. No serious concomitant disease, no active infections. Specifically, patients with autoimmune disease or organ allografts, and HBsAg or HIV positive patients are excluded.
16. Patients with a known allergy to shell fish (contains KLH) are excluded.
17. Patients with asthma or severe allergic disease necessitating medication are excluded
18. No pregnant or lactating women.

Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No