Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells.
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, I...
| Auteurs principaux: | , , , , , , , , |
|---|---|
| Format: | Journal article |
| Langue: | English |
| Publié: |
2000
|
| _version_ | 1826281782178217984 |
|---|---|
| author | Mackensen, A Herbst, B Chen, J Köhler, G Noppen, C Herr, W Spagnoli, G Cerundolo, V Lindemann, A |
| author_facet | Mackensen, A Herbst, B Chen, J Köhler, G Noppen, C Herr, W Spagnoli, G Cerundolo, V Lindemann, A |
| author_sort | Mackensen, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:33:59Z |
| format | Journal article |
| id | oxford-uuid:80c1fb3f-d4fb-42b2-b27e-0d2cfffab49b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:33:59Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:80c1fb3f-d4fb-42b2-b27e-0d2cfffab49b2022-03-26T21:25:38ZPhase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:80c1fb3f-d4fb-42b2-b27e-0d2cfffab49bEnglishSymplectic Elements at Oxford2000Mackensen, AHerbst, BChen, JKöhler, GNoppen, CHerr, WSpagnoli, GCerundolo, VLindemann, ADendritic 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. |
| spellingShingle | Mackensen, A Herbst, B Chen, J Köhler, G Noppen, C Herr, W Spagnoli, G Cerundolo, V Lindemann, A Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. |
| title | Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. |
| title_full | Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. |
| title_fullStr | Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. |
| title_full_unstemmed | Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. |
| title_short | Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. |
| title_sort | phase i study in melanoma patients of a vaccine with peptide pulsed dendritic cells generated in vitro from cd34 hematopoietic progenitor cells |
| work_keys_str_mv | AT mackensena phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT herbstb phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT chenj phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT kohlerg phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT noppenc phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT herrw phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT spagnolig phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT cerundolov phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells AT lindemanna phaseistudyinmelanomapatientsofavaccinewithpeptidepulseddendriticcellsgeneratedinvitrofromcd34hematopoieticprogenitorcells |