The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 402K)
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 Hege, K. M.
Right arrow Articles by Roberts, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hege, K. M.
Right arrow Articles by Roberts, M. R.
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?
© The Rockefeller University Press, 0022-1007/1996/12/2261/ $5.00
The Journal of Experimental Medicine, Volume 184, Number 6, December 1, 1996 2261-2270

Articles

Systemic T Cell–independent Tumor Immunity after Transplantation of Universal Receptor–modified Bone Marrow into SCID Mice

Kristen M. Hege, Keegan S. Cooke, Mitchell H. Finer, Krisztina M. Zsebo, and Margo R. Roberts

From the Department of Immunology and Cell Biology, Cell Genesys Inc., Foster City, California 94404

Gene modification of hematopoietic stem cells (HSC) with antigen-specific, chimeric, or "universal" immune receptors (URs) is a novel but untested form of targeted immunotherapy. A human immunodeficiency virus (HIV) envelope–specific UR consisting of the extracellular domain of human CD4 linked to the {zeta} chain of the T cell receptor (CD4{zeta}) was introduced ex vivo into murine HSC by retroviral transduction. After transplantation into immunodeficient SCID mice, sustained high level expression of CD4{zeta} was observed in circulating myeloid and natural killer cells. CD4{zeta}-transplanted mice were protected from challenge with a lethal dose of a disseminated human leukemia expressing HIV envelope. These results demonstrate the ability of chimeric receptors bearing {zeta}-signaling domains to activate non–T cell effector populations in vivo and thereby mediate systemic immunity.

Address correspondence to Dr. Margo R. Roberts, Director, Immunology and Cell Biology, Cell Genesys Inc., Foster City, CA 94404.

K.M. Hege was supported in part by the department of Hematology/Oncology, University of California, San Franciso School of Medicine.

1Abbreviations used in this paper: ADDC, antibody-dependent cytotoxicity; APC, allophycocyanin-streptavidin; FcR, Fc receptor; HIV-env, HIV envelope; HSC, hematopoietic stem cells; LDC, low density cells; PB, peripheral blood; Raji-env, Raji cells expressing HIV-env; SAb, singlechain antibody.

Data from this article were presented at the American society of Hematology meeting (Seattle, Washington, December, 1–5, 1995) and published in abstract form [1995. Blood. 86(Suppl. 1): 466a].


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