Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium  AACR Conference on Molecular Diagnostics - 2008
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

Cancer Research 67, 8450-8455, September 15, 2007. doi: 10.1158/0008-5472.CAN-07-1092
© 2007 American Association for Cancer Research

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chambers, B.
Right arrow Articles by van Hall, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chambers, B.
Right arrow Articles by van Hall, T.

Priority Reports

Induction of Protective CTL Immunity against Peptide Transporter TAP-Deficient Tumors through Dendritic Cell Vaccination

Benedict Chambers1, Per Grufman3, Vanoohi Fredriksson3, Kenth Andersson3, Marjet Roseboom4, Sandra Laban4, Marcel Camps4, Elisabeth Z. Wolpert2, Emmanuel J.H.J. Wiertz5, Rienk Offringa4, Hans-Gustaf Ljunggren1 and Thorbald van Hall6

1 Center for Infectious Medicine and 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet; 3 Accuro Immunology, Stockholm, Sweden; and Departments of 4 Immunohematology and Blood Transfusion, 5 Medical Microbiology, and 6 Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands

Requests for reprints: Benedict Chambers, Center for Infectious Medicine, F59, Department of Medicine, Karolinska University Hospital, Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden. E-mail: Benedict.Chambers{at}ki.se.

A large proportion of human cancers show deficiencies in the MHC class I antigen-processing machinery. Such defects render tumors resistant to immune eradication by tumoricidal CTLs. We recently identified a unique population of CTL that selectively targets tumor immune-escape variants through recognition of MHC-presented peptides, termed TEIPP (T cell epitopes associated with impaired peptide processing), expressed on cells lacking functional TAP-peptide transporters. Previously, we showed that vaccination with TEIPP peptides mediates protection against TAP-deficient tumors. Here, we further explored the concept of TEIPP-targeted therapy using a dendritic cell (DC)–based cellular vaccine. Impairment of TAP function in DC induced the presentation of endogenous TEIPP antigens by MHC class I molecules, and immunization with these DCs protected mice against the outgrowth of TAP-deficient lymphomas and fibrosarcomas. Immune analysis of vaccinated mice revealed strong TEIPP-specific CTL responses, and a crucial role for CD8+ cells in tumor resistance. Finally, we show that TEIPP antigens could be successfully induced in wild-type DC by introducing the viral TAP inhibitor UL49.5. Our results imply that immune intervention strategies with TAP-inhibited DC could be developed for the treatment of antigen processing–deficient cancers in humans. [Cancer Res 2007;67(18):8450–5]







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.