Immunotherapy with dendritic cells directed against tumor antigens shared with normal host cells results in severe autoimmune disease.
Vaccination with dendritic cells (DCs) presenting tumor antigens induces primary immune response or amplifies existing cytotoxic antitumor T cell responses. This study documents that antitumor treatment with DCs may cause severe autoimmune disease when the tumor antigens are not tumor-specific but are also expressed in peripheral nonlymphoid organs. Growing tumors with such shared tumor antigens that were, at least initially, strictly located outside of secondary lymphoid organs were successfully controlled by specific DC vaccination. However, antitumor treatment was accompanied by fatal autoimmune disease, i.e., autoimmune diabetes in transgenic mice expressing the tumor antigen also in pancreatic beta islet cells or by severe arteritis, myocarditis, and eventually dilated cardiomyopathy when arterial smooth muscle cells and cardiomyocytes expressed the transgenic tumor antigen. These results reveal the delicate balance between tumor immunity and autoimmunity and therefore point out important limitations for the use of not strictly tumor-specific antigens in antitumor vaccination with DCs.
Ludewig
B
B
Institute of Experimental Immunology, CH-8091 Zürich, Switzerland. ludewigb@pathol.unizh.ch
Ochsenbein
A F
AF
Odermatt
B
B
Paulin
D
D
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000209:etiology*; D019496:Cancer Vaccines / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D005354:Fibrosarcoma / Q000628:therapy*; D006023:Glycoproteins / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D008168:Lung / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000473:pathology; D009374:Neoplasms, Experimental / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects*; D001616:beta-Galactosidase / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006023:Glycoproteins; D010446:Peptide Fragments; D001616:beta-Galactosidase