adenovirus ccl-21 transduced mart-1/gp100/tyrosinase/ny-eso-1 peptide-pulsed dendritic cells matured

Conditions: Melanoma (Skin)

Summary: rationale: vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. purpose: this phase i trial is studying the side effects and best dose of vaccine therapy in treating patients with metastatic melanoma.

in this phase i study, patients will receive intradermal injections of adenovirus-ccl-21 transduced class i peptide-pulsed dc with total volumes for each intradermal injection of no more than 1 ml to be split into four injections of 0.25 ml each in four limbs in node draining areas (proximal arms and thighs), for a total dc dose of 2 x 10\^6, 10\^7 or 2 x 10\^7 cells to be administered intradermally. dc injections in one course of therapy will be given four times at intervals of weekly for two doses (days 1 and 8 +/- 72 hrs.), then every two weeks for two doses (at days 22 +/- 72 hrs. and 36 +/- 72 hours). cells will be harvested for dc administration and a flow cytometry analysis as well as microbiologic analysis including bacterial/fungal cultures and gram stain will be performed prior to infusion. all injections will be based on number of dc, not number of total cells.

Eligibility criteria:
inclusion criteria: * metastatic melanoma with measurable disease after attempted curative surgical therapy and who have received at least one prior chemotherapy regimen; adjuvant interferon or isolated limb perfusion is allowed. * tumor tissue must be available for immunohistochemical analysis, and specimens will stained for mart-1 by immunohistochemical staining and will also be stained for hmb-45 by immunohistochemistry, and positivity for at least one will be an entry requirement. * patients must be hla-a \*0201 positive, by a dna ssop analysis. * serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and alt/ast of less than 3x institutional upper limit of normal. * eastern cooperative oncology group (ecog) performance status of 0 or 1 * patients must be able to understand and sign an irb approved informed consent form. * patients must have white blood count of 3000 or greater, platelets of 100,000 or greater, and hemoglobin of 9.0 gm/dl or more. * patients with unresectable stages iii/iv uveal melanoma and metastatic mucosal melanoma will be eligible for this trial. exclusion criteria: * undergoing or have undergone in the past month any other therapy for their melanoma, including radiation therapy, chemotherapy and adjuvant therapy * have major systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular or respiratory systems, or have had a documented mi in the last 6 months * require steroid therapy * patients who are pregnant or lactating * known to be positive for hepatitis bsag, hepatitis c or hiv antibody * have a prior history of uveitis or autoimmune inflammatory eye disease * have had another malignancy other than cervical carcinoma-in-situ or basal cell /squamous cancer of the skin, unless they have undergone curative therapy more than 3 years ago and are still free of detectable disease, since the effects of peptide-pulsed dc on other active cancers are unknown

Keywords: stage iii melanoma stage iv melanoma recurrent melanoma mucosal melanoma