Effective tumor vaccines generated by in vitro modification of tumor cells with cytokines and bispecific monoclonal antibodies
Antitumor immune responses are mediated primarily by T cells 1 . Downregulation of the major histocompatiblity complex (MHC) and the molecules that costimulate the immune response is associated with defective signaling by tumor cells for T-cell activation 2–14 . In vitro treatment with a combination...
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Veröffentlicht in: | Nature medicine 1997-04, Vol.3 (4), p.451-455 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Antitumor immune responses are mediated primarily by T cells
1
. Downregulation of the major histocompatiblity complex (MHC) and the molecules that costimulate the immune response is associated with defective signaling by tumor cells for T-cell activation
2–14
.
In vitro
treatment with a combination of cytokines significantly increased the expression of MHC class I and adhesion molecules on tumor cell surfaces. When tumor cells were first incubated with a bispecific monoclonal antibody that binds antigen on tumor cells to CD28 on T cells, the modified tumor cells become immunogenic and are able to stimulate naive T cells, generating tumor-specific cytotoxic T cells
in vitro
. Immunization with the modified tumor cells elicits an immune response mediated by CD8
+
T cells. This response protected against a challenge with parental tumor cells and cured established tumors. The approach was effective in both low immunogenic and nonimmunogenic tumor model systems. Modification of tumor cells with this two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer immunotherapy. |
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ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/nm0497-451 |