Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests.
BACKGROUND
Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients.


METHODS
We evaluated the ability of mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide to induce CEA-specific T cell responses in patients with resectable liver metastases from colorectal cancer. CEA-specific T cell reactivity was monitored in peripheral blood, biopsies of vaccination sites and post-treatment DTH skin tests, and when available also in resected abdominal lymph nodes and tumor tissue.


RESULTS
Ten patients were vaccinated intradermally and intravenously with CEA-peptide pulsed mature DCs three times prior to resection of liver metastases. High numbers of CEA-specific T cells were detected in post-treatment DTH biopsies in seven out of 10 patients, which produced high amounts of interferon (IFN)-gamma upon stimulation with CEA-loaded target cells. These responses were not found in biopsies of first vaccination sites, indicating a de novo T cell induction or at least a strong potentiation by the vaccine. In addition, CEA-specific T cells were detected in a resected lymph node in one patient, but not in peripheral blood or tumor tissue.


CONCLUSIONS
Vaccination with CEA-peptide loaded mature DCs induced potent CEA-specific T cell responses in advanced colorectal cancer patients. In this study, antigen-specific T cell responses were readily detected in DTH skin tests, much less in abdominal lymph nodes, and not in peripheral blood and tumor tissue.
Lesterhuis
W J
WJ
Department of Medical Oncology, Nijmegen Centre for Molecular Life Sciences and Radboud University Nijmegen Medical Centre, The Netherlands.
de Vries
I J M
IJ
Schuurhuis
D H
DH
Boullart
A C I
AC
Jacobs
J F M
JF
de Boer
A J
AJ
Scharenborg
N M
NM
Brouwer
H M H
HM
van de Rakt
M W M M
MW
Figdor
C G
CG
Ruers
T J
TJ
Adema
G J
GJ
Punt
C J A
CJ
D000328:Adult; D019496:Cancer Vaccines / Q000008:administration & dosage; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000637:transplantation*; D004334:Drug Administration Schedule; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000556:secondary* / Q000601:surgery; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis; D008213:Lymphocyte Activation; D015166:Monitoring, Immunologic; D018579:Patient Selection; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen