The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 7 January 2002. doi:10.1084/jem.20011097
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 146K)
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 Dhodapkar, K. M.
Right arrow Articles by Dhodapkar, M. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dhodapkar, K. M.
Right arrow Articles by Dhodapkar, M. V.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Medline Plus Health Information
*Multiple Myeloma
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© Rockefeller University Press, 0022-1007/2002/1/125/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 1, January 7, 2002 125-133

Original Article

Antitumor Monoclonal Antibodies Enhance Cross-Presentation of Cellular Antigens and the Generation of Myeloma-specific Killer T Cells by Dendritic Cells

Kavita M. Dhodapkar1, Joseph Krasovsky1, Barbara Williamson3 and Madhav V. Dhodapkar1,2

1 Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, the
2 Department of Medicine, Memorial Sloan Kettering Cancer Center
3 Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan Kettering, New York, NY 10021

Address correspondence to Madhav Dhodapkar, Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: 212-327-8114; Fax: 212-327-8875; E-mail: dhodapm{at}mail.rockefeller.edu

The mechanism of antitumor effect of monoclonal antibodies (mAbs) is not fully understood. Here we show that coating myeloma cells with anti–syndecan-1 antibody promotes cross-presentation of cellular antigens by dendritic cells (DCs) to autologous T cells from healthy donors. The tumor cells treated with anti–syndecan-1 or isotype-matched control antibody were fed to HLA-mismatched monocyte-derived immature DCs. Tumor cell–loaded mature DCs induced a strong CD8+ T cell response that was specific for the cancer-testis (C-T) antigens expressed in the tumor. The CD8+ T cells killed peptide-pulsed targets, as well as myeloma tumor cells. Importantly, mAbs-coated tumor-loaded DCs were consistently superior to DCs loaded with peptides or dying cells for eliciting tumor-specific killer T cells. This enhanced cross-presentation was not due to enhanced tumor cell uptake or to DC maturation. When mixtures of NY-Eso-1-positive and -negative myeloma cells were captured by DCs, the anti–syndecan-1 antibody had to be on the NY-Eso-1-positive cells to elicit NY-Eso-1–specific response. Cross-presentation was inhibited by pretreatment of DCs with Fc{gamma} receptor blocking antibodies. Targeting of mAb-coated tumors to DCs may contribute to the efficacy of tumor-reactive mAb and offers a new strategy for immunotherapy.

Key Words: immunotherapy • myeloma • cancer-testis antigens • tumor immunity • Fc receptors


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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