Immunization of patients with malignant melanoma with autologous CD34 + cell-derived dendritic cells transduced ex vivo with a recombinant replication-deficient vaccinia vector encoding the human tyrosinase gene: A phase I trial

Massimo Di Nicola, Carmelo Carlo-Stella, Andrea Anichini, Roberta Mortarini, Anna Guidetti, Gabrina Tragni, Francesco Gallino, Michele Del Vecchio, Fernando Ravagnani, Daniele Morelli, Paul Chaplin, Nathaly Arndtz, Gerd Sutter, Ingo Drexler, Giorgia Parmiani, Natale Cascinelli, Alessandro M. Gianni

Research output: Contribution to journalArticle

Abstract

Protocol title: Immunization of Patients with Malignant Melanoma with Autologous CD34+ Cell-Derived Dendritic Cells Transduced Ex Vivo with a Recombinant Nonreplicating Vaccinia Vector Encoding the Human Tyrosinase Gene: A Phase I Trial. Study Phase: Phase I. Study Design: Nonrandomized, noncontrolled, single center. Study Objectives: Primary objective: Define the safety and toxicity of DCs/MVA-hTyr vaccine in patients with measurable metastatic melanoma. Secondary objectives: (1) to determine whether immunization with DCs/MVA-hTyr vaccine induces tyrosinase and melanoma-specific immune responses such as (a) development or enhancement of T lymphocyte-mediated responses in peripheral blood; (b) measurable delayed-type hypersensitivity (DTH) response in vivo; (c) development of antityrosinase antibodies in serum of treated patients; and (d) infiltration and expansion of tyrosinase-specific T lymphocytes in the inoculation site; and (2) to document any tumor regression and/or pigmentation modification that may result from immunization against tyrosinase. Number of Subjects: The total number of patients expected to complete this study is six. Study Population: Patients with malignant melanoma stage IV or high-risk stage III with measurable metastatic melanoma. Treatment Groups: Four vaccinations containing 100 X 106 DCs/MVA-hTyr will be given four times at 2-week intervals; the 1° vaccination will be given intravenously; the 2°, 3°, and 4° vaccinations will be given subcutaneously. Duration of Study: 20 weeks. Visit Schedule: Screening visit(s) Admission to the general clinical research center and baseline studies Preparative phase with the administration of filgrastim for six consecutive days followed by leukapheresis Immunization phase Follow-up visits monthly for 3 months and then at 2-month intervals for survival and general condition until death Safety parameters: Physical examination and measurements of melanoma lesions Complete blood tests Antimelanoma T lymphocyte (both CD8+ and CD4+) responses Ophthalmology evaluation including fundoscopy and visual acuity Neurological evaluation Cardiac rhythm, including Holter. Efficacy Parameters: Tumor response and time to progression by physical examination and CT scan Progression-free survival Overall survival Hypopigmentation Immunological evaluation: Melanoma antigen-specific and/or melanoma-specific CTL precursor frequency; antigen-specific HLA class II-restricted T cell responses; anti-tyrosinase antibodies in serum of treated patients; whenever possible biopsy at the site of vaccination to evaluate the infiltrate.

Original languageEnglish
Pages (from-to)1347-1360
Number of pages14
JournalHuman Gene Therapy
Volume14
Issue number14
DOIs
Publication statusPublished - Sep 20 2003

ASJC Scopus subject areas

  • Genetics

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