Induction of specific antitumor immunity in the mouse with the electrofusion product of tumor cells and dendritic cells

Dendritic cells (DCs) are potent antigen-presenting cells capable of inducing primary T-cell responses. Several immunotherapy treatment strategies involve manipulation of DCs, both in vivo and ex vivo, to promote the immunogenic presentation of tumor-associated antigens. In this study, an electrofus...

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Bibliographic Details
Published in:Molecular therapy 2003-04, Vol.7 (4), p.498-505
Main Authors: Siders, William M, Vergilis, Kristin L, Johnson, Carrie, Shields, Jacqueline, Kaplan, Johanne M
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Antigens, Neoplasm - metabolism
Bone marrow
Cancer Vaccines - immunology
Cell Fusion - methods
Cytotoxicity
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Electroporation
Gene therapy
Genetic engineering
Immunotherapy - methods
Kidney cancer
Lymphatic system
Melanoma
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Neoplasms, Experimental - immunology
Neoplasms, Experimental - prevention & control
Polyethylene glycol
T-Lymphocytes, Cytotoxic - immunology
Tumor Cells, Cultured
Tumors
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Summary:Dendritic cells (DCs) are potent antigen-presenting cells capable of inducing primary T-cell responses. Several immunotherapy treatment strategies involve manipulation of DCs, both in vivo and ex vivo, to promote the immunogenic presentation of tumor-associated antigens. In this study, an electrofusion protocol was developed to induce fusion between tumor cells and allogeneic bone marrow-derived DCs. Preimmunization with irradiated electrofusion product was found to provide partial to complete protection from tumor challenge in the murine Renca renal cell carcinoma model and the B16 and M3 melanoma models. Vaccinated survivors developed specific immunological memory and were able to reject a subsequent rechallenge with the same tumor cells but not a syngeneic unrelated tumor line. Antitumor protection in the B16 model was accompanied by the development of a polyclonal cytotoxic T-lymphocyte response against defined melanoma-associated antigens. The therapeutic potential of this type of approach was suggested by the ability of a Renca-DC electrofusion product to induce tumor rejection in a substantial percentage of hosts (60%) bearing pre-established tumor cells. These results indicate that treatment with electrofused tumor cells and allogeneic DCs is capable of inducing a potent antitumor response and could conceivably be applied to a wide range of cancer indications for which tumor-associated antigens have not been identified.
ISSN:1525-0016
1525-0024
DOI:10.1016/S1525-0016(03)00044-3