This article seems relevant to the Dana-Farber dentritic cell fusion technique used in the brest cancer vaccine. Aren't cancer cells likely to share some antigens with non-cancer cells?
Jason
Published online 28 February 2000
¸ The Rockefeller University Press, /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 Ludewiga, Adrian F. Ochsenbeina, Bernhard Odermatta, Denise Paulinb, Hans Hengartnera, and Rolf M. Zinkernagela
a Institute of Experimental Immunology, CH-8091 Zrich, Switzerland
b Universit‚ Paris 7, 75005 Paris, France
Correspondence to: Burkhard Ludewig, Institute of Experi-mental Immunology, Dept. of Pathology, University of Zrich, Schmelzbergstr. 12, CH-8091 Zrich, Switzerland. Tel:41-1-255-2989 Fax:41-1-255-4420 E-mail:ludewigb@pathol.unizh.ch.
Released online: 28 February 2000
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 á 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.
Key Words: dendritic cells, immunotherapy, autoimmunity, tumor immunity, vaccination
This article has been cited by other articles:
Dubinett, S. M., Batra, R. K., Miller, P. W., Sharma, S. (2000). Tumor Antigens in Thoracic Malignancy. Am J Respir Cell Mol Biol 22: 524-527 |
