TY - JOUR
T1 - In situ expression of tumor antigens by messenger RNA-electroporated dendritic cells in lymph nodes of melanoma patients
AU - Schuurhuis, Danita H
AU - Verdijk, Pauline
AU - Schreibelt, Gerty
AU - Aarntzen, Erik H J G
AU - Scharenborg, Nicole
AU - de Boer, Annemiek
AU - van de Rakt, Mandy W M M
AU - Kerkhoff, Marieke
AU - Gerritsen, Marie-Jeanne P
AU - Eijckeler, Femke
AU - Bonenkamp, Johannes J
AU - Blokx, Willeke
AU - van Krieken, J Han
AU - Boerman, Otto C
AU - Oyen, Wim J G
AU - Punt, Cornelis J A
AU - Figdor, Carl G
AU - Adema, Gosse J
AU - de Vries, I Jolanda M
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) for cancer immunotherapy has been proved efficient and clinically safe. It obviates prior knowledge of CTL and Th epitopes in the antigen and leads to the presentation of multiple epitopes for several HLA alleles. Here we studied the migration capacity and the antigen expression of mRNA-electroporated DC (mRNA-DC) in lymph nodes after vaccination in melanoma patients. DC were electroporated with mRNA encoding gp100 or tyrosinase, labeled with indium-111 and superparamagnetic iron oxide particles, and injected intranodally in melanoma patients 24 to 48 hours before scheduled dissection of regional lymph nodes. Immunohistochemical analysis of the lymph nodes after surgery revealed that mRNA-DC migrated from the injection site into the T-cell areas of the same and subsequent lymph nodes, where they expressed the antigen encoded by the electroporated mRNA. Furthermore, vaccine-related CD8(+) T-cell responses could be detected in 7 of 11 patients vaccinated with mRNA-DC. Together these data show that mature DC electroporated with mRNA encoding TAA migrate and express antigens in the lymph nodes and induce specific immune responses.
AB - Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) for cancer immunotherapy has been proved efficient and clinically safe. It obviates prior knowledge of CTL and Th epitopes in the antigen and leads to the presentation of multiple epitopes for several HLA alleles. Here we studied the migration capacity and the antigen expression of mRNA-electroporated DC (mRNA-DC) in lymph nodes after vaccination in melanoma patients. DC were electroporated with mRNA encoding gp100 or tyrosinase, labeled with indium-111 and superparamagnetic iron oxide particles, and injected intranodally in melanoma patients 24 to 48 hours before scheduled dissection of regional lymph nodes. Immunohistochemical analysis of the lymph nodes after surgery revealed that mRNA-DC migrated from the injection site into the T-cell areas of the same and subsequent lymph nodes, where they expressed the antigen encoded by the electroporated mRNA. Furthermore, vaccine-related CD8(+) T-cell responses could be detected in 7 of 11 patients vaccinated with mRNA-DC. Together these data show that mature DC electroporated with mRNA encoding TAA migrate and express antigens in the lymph nodes and induce specific immune responses.
KW - Antigens, Neoplasm/biosynthesis
KW - CD8-Positive T-Lymphocytes/immunology
KW - Dendritic Cells/immunology
KW - Electroporation/methods
KW - HLA-A2 Antigen/immunology
KW - Humans
KW - Immunotherapy, Adoptive/methods
KW - Indium Radioisotopes
KW - Lymph Nodes/immunology
KW - Lymphocyte Activation
KW - Melanoma/immunology
KW - RNA, Messenger/genetics
U2 - 10.1158/0008-5472.CAN-08-3920
DO - 10.1158/0008-5472.CAN-08-3920
M3 - Article
C2 - 19318559
SN - 0008-5472
VL - 69
SP - 2927
EP - 2934
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -