Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients

Radboud University Medical Center

Status and phase: Completed; Phase 2; Phase 1

Conditions: Melanoma Stage III or IV

Treatments: Biological: autologous dendritic cell vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT00243529

2003-2917

KWF 2003-2917

Details and patient eligibility

About

Dendritic cells (DCs)are the most potent antigen-presenting cells of the immune system, as such they are able to direct the immune system specifically against cancer cells. Currently DCs are used in clinical vaccination studies and immunological and clinical responses have been observed. For inducing anti-tumor immunity, the DCs have to be loaded with tumor antigen (i.e. molecular structures that are presented by the tumor, that are recognized by the immune system). Currently most studies use tumor peptides (small protein fragments) for this purpose. This approach has several disadvantages: only patients with a certain HLA-type can be treated and the immune response that is induced by the vaccine is limited to the used peptides. These disadvantages do not exist when the DCs present antigen which is endogenously processed, for example after RNA transfection. For this reason we investigate the immunogenicity of DCs that are pulsed with peptides or transfected with mRNA encoding melanoma associated antigens in stage III and IV melanoma patients.

Enrollment: 64 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

For both stage III and IV

• Histological proof of cutaneous melanoma
• Melanoma expressing both gp100 and tyrosinase, each in approximately 20% or more of cells by immunohistochemistry staining,
• HLA type A2 and/or A3, with known HLA-DR4 expression,
• 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.
• Expected adequacy of follow-up,
• Written informed consent.

For Stage III only

• Stage III melanoma according to the 2001 AJCC criteria.
• Start of treatment within 2 months of lymph node dissection for melanoma stage III

For stage IV only

-Stage IV melanoma according to the 2001 AJCC criteria. Limited tumor burden; LDH < 2x upper limit of normal

Exclusion criteria

For both stage III and IV

• No autoimmune disorders, no concomitant use of immunosuppressive drugs,
• no serious concomitant disease, no serious active infections, no other malignancy in the past 5 years with the exception of curatively treated carcinoma in-situ of the cervix/squamous cell carcinoma of the skin,
• No known allergy to shell fish (contains KLH) are excluded.
• No pregnancy or lactation,

For stage III only:

• No signs or symptoms of distant metastases as defined by normal history, physical examination, chest X-ray and serum LDH.
• No concomitant or previous systemic treatment for melanoma

For stage IV only:

• No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases, a CT scan of the brain should be performed to exclude this.
• No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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64 participants in 3 patient groups

MHC Class I restricted epitopes

Active Comparator group

Description:

HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase

Treatment:

Biological: autologous dendritic cell vaccine

MHC Class I and II restricted epitopes

Experimental group

Description:

HLA-A2.1 and HLA-DR4 patients are vaccinated with dendritic cells loaded with MHC Class I and II restricted epitopes of tumor antigens gp100 and tyrosinase

Treatment:

Biological: autologous dendritic cell vaccine

mRNA transfected DC

Experimental group

Description:

HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase

Treatment:

Biological: autologous dendritic cell vaccine