Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination with altered peptide ligand-loaded dendritic cells.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Babatz
Jana
J
Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
Röllig
Christoph
C
Löbel
Bärbel
B
Folprecht
Gunnar
G
Haack
Michael
M
Günther
Heinrich
H
Köhne
Claus-Henning
CH
Ehninger
Gerhard
G
Schmitz
Marc
M
Bornhäuser
Martin
M
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D015179:Colorectal Neoplasms / Q000628:therapy*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D018189:Immunomagnetic Separation; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D010455:Peptides; D007371:Interferon-gamma