Immunotherapy with Dendritic Cells Directed against Tumor Antigens Shared with Normal Host Cells Results in Severe Autoimmune Disease

doi:10.1084/jem.191.5.795

Published online 28 February 2000.

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© The Rockefeller University Press, 0022-1007/2000/3/795/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 5, March 6, 2000 795-804

Original Article

Immunotherapy with Dendritic Cells Directed against Tumor Antigens Shared with Normal Host Cells Results in Severe Autoimmune Disease

Burkhard Ludewig^a, Adrian F. Ochsenbein^a, Bernhard Odermatt^a, Denise Paulin^b, Hans Hengartner^a, and Rolf M. Zinkernagel^a
^a Institute of Experimental Immunology, CH-8091 Zürich, Switzerland
^b Université Paris 7, 75005 Paris, France

Correspondence to: Burkhard Ludewig, Institute of Experi-mental Immunology, Dept. of Pathology, University of Zürich, Schmelzbergstr. 12, CH-8091 Zürich, Switzerland. Tel:41-1-255-2989 Fax:41-1-255-4420 E-mail:ludewigb{at}pathol.unizh.ch.

Released online: 28 February 2000

Vaccination with dendritic cells (DCs) presenting tumor antigensinduces primary immune response or amplifies existing cytotoxicantitumor T cell responses. This study documents that antitumortreatment with DCs may cause severe autoimmune disease whenthe tumor antigens are not tumor-specific but are also expressedin peripheral nonlymphoid organs. Growing tumors with such sharedtumor antigens that were, at least initially, strictly locatedoutside of secondary lymphoid organs were successfully controlledby specific DC vaccination. However, antitumor treatment wasaccompanied by fatal autoimmune disease, i.e., autoimmune diabetesin transgenic mice expressing the tumor antigen also in pancreaticß islet cells or by severe arteritis, myocarditis, andeventually dilated cardiomyopathy when arterial smooth musclecells and cardiomyocytes expressed the transgenic tumor antigen.These results reveal the delicate balance between tumor immunityand autoimmunity and therefore point out important limitationsfor the use of not strictly tumor-specific antigens in antitumorvaccination with DCs.

Key Words: dendritic cells, immunotherapy, autoimmunity, tumor immunity,vaccination

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