Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells.
OBJECTIVE
To demonstrate the feasibility of inducing tumor antigen-specific immune responses in patients with metastatic cancer using total tumor RNA-loaded dendritic cells (DCs).


BACKGROUND
The authors have shown that DCs transfected with mRNA encoding defined tumor antigens induce tumor antigen-specific T-cell responses in vitro and in vivo. There may be significant advantages to inducing immune responses against the entire repertoire of antigens expressed by a patient's autologous tumor.


METHODS
RNA was extracted from a metastatic colon cancer and used to load autologous DCs. The DCs were coincubated with autologous T cells and the cytolytic activity of the T cells was assessed by the ability to lyse the autologous tumor cells. RNA was then extracted from a metastatic lung cancer and used to load autologous DCs, followed by four injections of the DC vaccine given every 4 weeks. Tumor antigen-specific cytotoxic T lymphocyte activity was then evaluated by testing peripheral blood mononuclear cells for their ability to lyse an antigen-expressing target.


RESULTS
DCs transfected with the total RNA content of autologous tumor cells stimulated antigen-specific T-cell responses that are capable of recognizing and lysing autologous, primary tumor cells in vitro. Tumor-specific immune responses were induced in a patient with a carcinoembryonic antigen-expressing adenocarcinoma after immunization with autologous DCs transfected with total tumor RNA.


CONCLUSIONS
DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of tumor antigens of surgically resected malignancies.
Nair
Smita K
SK
Center for Genetic and Cellular Therapies, Duke University Medical Center, Durham, North Carolina 27710, USA.
Morse
Michael
M
Boczkowski
David
D
Cumming
R Ian
RI
Vasovic
Ljiljana
L
Gilboa
Eli
E
Lyerly
H Kim
HK
D000230:Adenocarcinoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D005240:Feasibility Studies; D006801:Humans; D016233:Immunotherapy, Active; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology
D000951:Antigens, Neoplasm