PMID- 16034561
OWN - NLM
STAT- MEDLINE
DCOM- 20060623
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 55
IP  - 3
DP  - 2006 Mar
TI  - Induction of cellular immune responses against carcinoembryonic antigen in 
      patients with metastatic tumors after vaccination with altered peptide 
      ligand-loaded dendritic cells.
PG  - 268-76
AB  - PURPOSE: Dendritic cells (DCs) are characterized by their extraordinary capacity 
      to induce T-cell responses, providing the opportunity of DC-based cancer 
      vaccination protocols. In the present study, we conducted a phase I/II clinical 
      trial to determine the capability of DCs differentiated from immunomagnetically 
      isolated CD14+ monocytes and pulsed with a carcinoembryonic antigen-derived 
      altered peptide (CEAalt) to induce specific CD8+ T cells in cancer patients. 
      EXPERIMENTAL DESIGN: Nine patients with CEA-positive colorectal cancer (n=7) or 
      lung cancer (n=2) were enrolled in this study. Autologous CD14+ monocytes were 
      isolated by large-scale immunomagnetic separation and differentiated to mature 
      DCs in sufficient numbers and at high purity. After incubation with the CEAalt 
      peptide and keyhole limpet hemocyanin, DCs were administered to patients 
      intravenously at dose levels of 1 x 10(7) and 5 x 10(7) cells. Patients received 
      four immunizations every second week. RESULTS: ELISPOT analysis revealed a 
      vaccine-induced increase in the number of CEAalt peptide-specific Interferon 
      (IFN)-gamma producing CD8+ T cells in five of nine patients and of CD8+ T 
      lymphocytes recognizing the native CEA peptide in three of nine patients. In 
      addition, CD8+ T lymphocytes derived from one patient exhibiting an immunological 
      response after vaccination efficiently lysed peptide-loaded T2 cells and tumor 
      cells. Immunization was well tolerated by all patients without severe signs of 
      toxicity. CONCLUSION: Vaccination with CEAalt-pulsed DCs derived from 
      immunomagnetically isolated CD14+ monocytes efficiently expand peptide-specific 
      CD8+ T lymphocytes in vivo and may be a promising alternative for cancer 
      immunotherapy.
FAU - Babatz, Jana
AU  - Babatz J
AD  - Medizinische Klinik und Poliklinik I, Universitatsklinikum Dresden, Fetscherstr. 
      74, 01307, Dresden, Germany.
FAU - Rollig, Christoph
AU  - Rollig C
FAU - Lobel, Barbel
AU  - Lobel B
FAU - Folprecht, Gunnar
AU  - Folprecht G
FAU - Haack, Michael
AU  - Haack M
FAU - Gunther, Heinrich
AU  - Gunther H
FAU - Kohne, Claus-Henning
AU  - Kohne CH
FAU - Ehninger, Gerhard
AU  - Ehninger G
FAU - Schmitz, Marc
AU  - Schmitz M
FAU - Bornhauser, Martin
AU  - Bornhauser M
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20050721
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Cancer Vaccines)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Peptides)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/*immunology
MH  - Carcinoembryonic Antigen/*immunology
MH  - Cell Differentiation/immunology
MH  - Colorectal Neoplasms/*therapy
MH  - Dendritic Cells/cytology/*immunology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunity, Cellular
MH  - Immunomagnetic Separation
MH  - Interferon-gamma/immunology/metabolism
MH  - Ligands
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Lung Neoplasms/*therapy
MH  - Male
MH  - Middle Aged
MH  - Monocytes/cytology/immunology/metabolism
MH  - Peptides/immunology/therapeutic use
PMC - PMC11031026
EDAT- 2005/07/22 09:00
MHDA- 2006/06/24 09:00
PMCR- 2005/07/21
CRDT- 2005/07/22 09:00
PHST- 2005/01/10 00:00 [received]
PHST- 2005/05/03 00:00 [accepted]
PHST- 2005/07/22 09:00 [pubmed]
PHST- 2006/06/24 09:00 [medline]
PHST- 2005/07/22 09:00 [entrez]
PHST- 2005/07/21 00:00 [pmc-release]
AID - 21 [pii]
AID - 10.1007/s00262-005-0021-x [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2006 Mar;55(3):268-76. doi: 10.1007/s00262-005-0021-x. 
      Epub 2005 Jul 21.