PMID- 10760827
OWN - NLM
STAT- MEDLINE
DCOM- 20000502
LR  - 20210102
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 86
IP  - 3
DP  - 2000 May 1
TI  - Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic 
      cells generated in vitro from CD34(+) hematopoietic progenitor cells.
PG  - 385-92
AB  - 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.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Mackensen, A
AU  - Mackensen A
AD  - Department of Hematology/Oncology, Freiburg University Medical Center, Freiburg, 
      Germany. andreas.mackensen@klinik.uni-regensburg.de
FAU - Herbst, B
AU  - Herbst B
FAU - Chen, J L
AU  - Chen JL
FAU - Kohler, G
AU  - Kohler G
FAU - Noppen, C
AU  - Noppen C
FAU - Herr, W
AU  - Herr W
FAU - Spagnoli, G C
AU  - Spagnoli GC
FAU - Cerundolo, V
AU  - Cerundolo V
FAU - Lindemann, A
AU  - Lindemann A
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, CD34)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Peptides)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - *Antigen Presentation
MH  - Antigens, CD34
MH  - Antigens, Neoplasm
MH  - Cancer Vaccines/*administration & dosage/immunology
MH  - Cell Differentiation/immunology
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology/pathology/transplantation
MH  - Female
MH  - Hematopoietic Stem Cells/immunology/pathology
MH  - Humans
MH  - *Immunotherapy, Adoptive
MH  - Male
MH  - Melanoma/*immunology/*therapy
MH  - Middle Aged
MH  - Peptides/immunology
MH  - Pilot Projects
EDAT- 2000/04/13 09:00
MHDA- 2000/05/08 09:00
CRDT- 2000/04/13 09:00
PHST- 2000/04/13 09:00 [pubmed]
PHST- 2000/05/08 09:00 [medline]
PHST- 2000/04/13 09:00 [entrez]
AID - 10.1002/(SICI)1097-0215(20000501)86:3<385::AID-IJC13>3.0.CO;2-T [pii]
AID - 10.1002/(sici)1097-0215(20000501)86:3<385::aid-ijc13>3.0.co;2-t [doi]
PST - ppublish
SO  - Int J Cancer. 2000 May 1;86(3):385-92. doi: 
      10.1002/(sici)1097-0215(20000501)86:3<385::aid-ijc13>3.0.co;2-t.