The Journal of Experimental Medicine
PBL InterferonSource
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 25 October 2004 doi:10.1084/jem.20040327
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 9, 1157-1165
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 611K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bondanza, A.
Right arrow Articles by Herrmann, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bondanza, A.
Right arrow Articles by Herrmann, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Inhibition of Phosphatidylserine Recognition Heightens the Immunogenicity of Irradiated Lymphoma Cells In Vivo

Attilio Bondanza1, Valérie S. Zimmermann1, Patrizia Rovere-Querini1, Javier Turnay2, Ingrid E. Dumitriu1,3, Christian M. Stach3, Reinhard E. Voll3, Udo S. Gaipl3, Wolf Bertling6, Ernst Pöschl4, Joachim R. Kalden3, Angelo A. Manfredi1, and Martin Herrmann3,5

1 Clinical Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, H. San Raffaele Scientific Institute and Vita-Salute University, 20132 Milano, Italy
2 Departamento de Bioquimica y Biologia Molecular I, Facultad de Ciencias Quimicas, Universidad Complutense, 28040 Madrid, Spain
3 Department of Internal Medicine III, Institute for Clinical Immunology and Rheumatology
4 Department of Experimental Medicine I, Friedrich-Alexander University of Erlangen-Nuremberg
5 Responsif GmbH, 91054 Erlangen, Germany
6 November AG, 91056 Erlangen, Germany

Address correspondence to Angelo Manfredi, Clinical Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, H. San Raffaele Institute, DIBIT 3A1, via Olgettina 58, 20132 Milano, Italy. Phone: 39-02-2643-4864; Fax: 39-02-2643-4786; email: manfredi.angelo{at}hsr.it

Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages. Here, we report that AxV preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in vivo clearance, elicits the release of proinflammatory cytokines and dramatically enhances the protection elicited against the tumor. The response was endowed with both memory, because protected animals rejected living lymphoma cells after 72 d, and specificity, because vaccinated animals failed to reject unrelated neoplasms. Finally, AxV–coupled irradiated cells induced the regression of growing tumors. These data indicate that endogenous adjuvants that bind to dying tumor cells can be exploited to target tumors for immune rejection.

Key Words: apoptosis • phagocytosis • cancer • adjuvants • dendritic cells

A. Bondanza and V.S. Zimmermann contributed equally to this paper.

Abbreviations used in this paper: AxV, annexin V; ITC, irradiated tumor cell; M{phi}, macrophages; PS, phosphatidylserine.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS