Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells.

Journal article

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that can be used for vaccination purposes, to induce a specific T-cell response in vivo against melanoma-associated antigens. We have shown that the sequential use of early-acting hematopoietic growth factors, stem cell factor, IL-3 and IL-6, followed by differentiation with IL-4 and granulocyte-macrophage colony-stimulating factor allows the in vitro generation of large numbers of immature DCs from CD34(+) peripheral blood progenitor cells. Maturation to interdigitating DCs could specifically be induced within 24 hr by addition of TNF-alpha. Here, we report on a phase I clinical vaccination trial in melanoma patients using peptide-pulsed DCs. Fourteen HLA-A1(+) or HLA-A2(+) patients received at least 4 i.v. infusions of 5 x 10(6) to 5 x 10(7) DCs pulsed with a pool of peptides including either MAGE-1, MAGE-3 (HLA-A1) or Melan-A, gp100, tyrosinase (HLA-A2), depending on the HLA haplotype. A total of 83 vaccinations were performed. Clinical side effects were mild and consisted of low-grade fever (WHO grade I-II). Clinical and immunological responses consisted of anti-tumor responses in 2 patients, increased melanoma peptide-specific delayed-type hypersensitivity reactions in 4 patients, significant expansion of Melan-A- and gp100-specific cytotoxic T lymphocytes in the peripheral blood lymphocytes of 1 patient after vaccination and development of vitiligo in another HLA-A2(+) patient. Our data indicate that the vaccination of peptide-pulsed DCs is capable of inducing clinical and systemic tumor-specific immune responses without provoking major side effects.

Authors: Mackensen, A; Herbst, B; Chen, J; Köhler, G; Noppen, C

• Publication status: Published
• Journal: International journal of cancer. Journal international du cancer
• Volume: 86
• Issue: 3
• Pages: 385-392
• Publication date: 2000-05-01
• DOI: 10.1002/(sici)1097-0215(20000501)86:3<385::aid-ijc13>3.0.co;2-t
• EISSN: 1097-0215
• ISSN: 0020-7136
• Language: English
• Keywords: Female; Humans; Adolescent; Antigens, Neoplasm; Cytotoxicity, Immunologic; Hematopoietic Stem Cells; Immunotherapy, Adoptive; Cancer Vaccines; Middle Aged; Adult; Male; Antigens, CD34; Melanoma; Aged; Pilot Projects; Dendritic Cells; Antigen Presentation; Peptides; Cell Differentiation