The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

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
Right arrow Citation Map
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Roberts, M. R.
Right arrow Articles by Finer, M. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roberts, M. R.
Right arrow Articles by Finer, M. H.
The Journal of Immunology, 1998, 161: 375-384.
Copyright © 1998 by The American Association of Immunologists

Antigen-Specific Cytolysis by Neutrophils and NK Cells Expressing Chimeric Immune Receptors Bearing {zeta} or {gamma} Signaling Domains

Margo R. Roberts1, Keegan S. Cooke2, Annie-Chen Tran, Kent A. Smith3, Wei Yu Lin, Martin Wang4, Thomas J. Dull, Deborah Farson, Krisztina M. Zsebo5 and Mitchell H. Finer

Cell Genesys Inc., Foster City, CA 94404

TCR- and IgG-binding Fc receptors (Fc{gamma}R) mediate a variety of critical biologic activities including cytolysis via the structurally related {zeta}- and {gamma}-chains. In previous studies, we have described chimeric immune receptors (CIR) in which the ligand-binding domain of a heterologous receptor or Ab is fused directly to the cytoplasmic domain of the TCR {zeta}-chain. Such {zeta}-CIRs efficiently trigger cytotoxic function of both T and NK cells in a target-specific manner. In this report, we compared the ability of both {zeta}- and {gamma}-CIRs to activate the cytolytic function of two distinct classes of Fc{gamma}R-bearing effectors, NK cells and neutrophils. Mature neutrophils expressing {zeta}- and {gamma}-CIR were generated in vivo from murine hemopoietic stem cells following transplantation of syngeneic mice with retrovirally transduced bone marrow or in vitro from transduced human CD34+ progenitors following differentiation. Both {zeta}- and {gamma}-based CIRs were capable of activating target-specific cytolysis by both NK cells and neutrophils, although the {zeta}-CIR was consistently more efficient. The experimental approach described is a powerful one with which to study the role of nonlymphoid effector cells in the host immune system and permits the rational design of immunotherapeutic strategies that rely on harnessing multiple immune cell functions via CIR-modified hemopoietic stem cells or progenitors.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
H. J. Pegram, J. T. Jackson, M. J. Smyth, M. H. Kershaw, and P. K. Darcy
Adoptive Transfer of Gene-Modified Primary NK Cells Can Specifically Inhibit Tumor Progression In Vivo
J. Immunol., September 1, 2008; 181(5): 3449 - 3455.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Imai, S. Iwamoto, and D. Campana
Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells
Blood, July 1, 2005; 106(1): 376 - 383.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. De Palma, E. Montini, F. R. S. de Sio, F. Benedicenti, A. Gentile, E. Medico, and L. Naldini
Promoter trapping reveals significant differences in integration site selection between MLV and HIV vectors in primary hematopoietic cells
Blood, March 15, 2005; 105(6): 2307 - 2315.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. I. McFarland, S. A. Hansal, D. I. Morris, D. W. McVicar, P. E. Love, and A. S. Rosenberg
Signaling through MHC in transgenic mice generates a population of memory phenotype cytolytic cells that lack TCR
Blood, June 1, 2003; 101(11): 4520 - 4528.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. M. Haynes, J. A. Trapani, M. W. L. Teng, J. T. Jackson, L. Cerruti, S. M. Jane, M. H. Kershaw, M. J. Smyth, and P. K. Darcy
Rejection of Syngeneic Colon Carcinoma by CTLs Expressing Single-Chain Antibody Receptors Codelivering CD28 Costimulation
J. Immunol., November 15, 2002; 169(10): 5780 - 5786.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
W. Y. Lin and M. R. Roberts
Developmental dissociation of T cells from B, NK, and myeloid cells revealed by MHC class II-specific chimeric immune receptors bearing TCR-zeta or FcR-gamma chain signaling domains
Blood, September 26, 2002; 100(8): 3045 - 3048.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Uherek, T. Tonn, B. Uherek, S. Becker, B. Schnierle, H.-G. Klingemann, and W. Wels
Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction
Blood, July 30, 2002; 100(4): 1265 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. M. Haynes, M. B. Snook, J. A. Trapani, L. Cerruti, S. M. Jane, M. J. Smyth, and P. K. Darcy
Redirecting Mouse CTL Against Colon Carcinoma: Superior Signaling Efficacy of Single-Chain Variable Domain Chimeras Containing TCR-{{zeta}} vs Fc{{epsilon}}RI-{{gamma}}
J. Immunol., January 1, 2001; 166(1): 182 - 187.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. F. Nolan, C.-O. Yun, Y. Akamatsu, J. C. Murphy, S.-O. Leung, E. J. Beecham, and R. P. Junghans
Bypassing Immunization: Optimized Design of ""Designer T Cells"" against Carcinoembryonic Antigen (CEA)-expressing Tumors, and Lack of Suppression by Soluble CEA
Clin. Cancer Res., December 1, 1999; 5(12): 3928 - 3941.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.