Mackensen, Andreas and Herbst, Birgit and Chen, Ji-Li and Koehler, Gabriele and Noppen, Christoph and Herr, Wolfgang and Spagnoli, Giulio C. and Cerundolo, Vincenzo and Lindemann, Albrecht (2000) Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. INTERNATIONAL JOURNAL OF CANCER, 86 (3). pp. 385-392. ISSN 0020-7136
Full text not available from this repository. (Request a copy)Abstract
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 MACE-I, 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 I 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. (C) 2000 Wiley-Liss, Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIGEN-PRESENTING CELLS; CYTOTOXIC T-LYMPHOCYTES; PERIPHERAL-BLOOD; METASTATIC MELANOMA; LOW-FREQUENCY; IMMUNIZATION; INDUCTION; ENHANCEMENT; IMMUNITY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 May 2022 07:03 |
| Last Modified: | 10 May 2022 07:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42520 |
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