|
|
Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-04-1041.
Submitted April 4, 2002
Accepted June 17, 2002
Single-chain antigen recognition receptors that co-stimulate potent rejection of established experimental tumors
Nicole M Haynes, Joseph A Trapani, Michele W L Teng, Jacob T Jackson, Stephen M Jane, Loretta Cerutti, Michael H Kershaw, Mark J Smyth, and Phillip K Darcy*
Cancer Immunology, Peter MacCallum Cancer Institute, Melbourne, VIC, Australia
Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia
* Corresponding author; email: p.darcy{at}pmci.unimelb.edu.au.
Tumor cells are usually weakly immunogenic as they largely express self-antigens and can down-regulate major histocompatability complex/peptide molecules and critical co-stimulatory ligands. The challenge for immunotherapies has been to provide vigorous immune effector cells that circumvent these tumor escape mechanisms and eradicate established tumors. One promising approach is to engineer T cells with single chain antibody receptors, and since T cells require two distinct signals for optimal activation, we have compared therapeutic efficacy of erbB2-reactive chimeric receptors that contain either TCR- or CD28/TCR- signaling domains. We have demonstrated that primary mouse CD8+ T lymphocytes expressing the scFv-CD28- receptor have a greater capacity to secrete Tc1 cytokines, induce T-cell proliferation, and inhibit established tumor growth and metastases in vivo. The suppression of established tumor burden by cytotoxic T cells expressing the CD28/TCR- chimera was critically dependent upon their IFN- secretion. Our study has illustrated the practical advantage of engineering a T cell signaling complex that co-delivers CD28 activation, dependent only upon the tumors expression of the appropriate tumor associated antigen.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Yvon, M. Del Vecchio, B. Savoldo, V. Hoyos, A. Dutour, A. Anichini, G. Dotti, and M. K. Brenner
Immunotherapy of Metastatic Melanoma Using Genetically Engineered GD2-Specific T cells
Clin. Cancer Res.,
September 15, 2009;
15(18):
5852 - 5860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Carpenito, M. C. Milone, R. Hassan, J. C. Simonet, M. Lakhal, M. M. Suhoski, A. Varela-Rohena, K. M. Haines, D. F. Heitjan, S. M. Albelda, et al.
Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains
PNAS,
March 3, 2009;
106(9):
3360 - 3365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C.R. Emtage, A. S.Y. Lo, E. M. Gomes, D. L. Liu, R. M. Gonzalo-Daganzo, and R. P. Junghans
Second-Generation Anti-Carcinoembryonic Antigen Designer T Cells Resist Activation-Induced Cell Death, Proliferate on Tumor Contact, Secrete Cytokines, and Exhibit Superior Antitumor Activity In vivo: A Preclinical Evaluation
Clin. Cancer Res.,
December 15, 2008;
14(24):
8112 - 8122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wilkie, G. Picco, J. Foster, D. M. Davies, S. Julien, L. Cooper, S. Arif, S. J. Mather, J. Taylor-Papadimitriou, J. M. Burchell, et al.
Retargeting of Human T Cells to Tumor-Associated MUC1: The Evolution of a Chimeric Antigen Receptor
J. Immunol.,
April 1, 2008;
180(7):
4901 - 4909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Moeller, M. H. Kershaw, R. Cameron, J. A. Westwood, J. A. Trapani, M. J. Smyth, and P. K. Darcy
Sustained Antigen-Specific Antitumor Recall Response Mediated by Gene-Modified CD4+ T Helper-1 and CD8+ T Cells
Cancer Res.,
December 1, 2007;
67(23):
11428 - 11437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Ahmed, M. Ratnayake, B. Savoldo, L. Perlaky, G. Dotti, W. S. Wels, M. B. Bhattacharjee, R. J. Gilbertson, H. D. Shine, H. L. Weiss, et al.
Regression of Experimental Medulloblastoma following Transfer of HER2-Specific T Cells
Cancer Res.,
June 15, 2007;
67(12):
5957 - 5964.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Kowolik, M. S. Topp, S. Gonzalez, T. Pfeiffer, S. Olivares, N. Gonzalez, D. D. Smith, S. J. Forman, M. C. Jensen, and L. J.N. Cooper
CD28 Costimulation Provided through a CD19-Specific Chimeric Antigen Receptor Enhances In vivo Persistence and Antitumor Efficacy of Adoptively Transferred T Cells.
Cancer Res.,
November 15, 2006;
66(22):
10995 - 11004.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Kershaw, J. A. Westwood, L. L. Parker, G. Wang, Z. Eshhar, S. A. Mavroukakis, D. E. White, J. R. Wunderlich, S. Canevari, L. Rogers-Freezer, et al.
A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer.
Clin. Cancer Res.,
October 15, 2006;
12(20):
6106 - 6115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Schaft, B. Lankiewicz, J. Drexhage, C. Berrevoets, D. J. Moss, V. Levitsky, M. Bonneville, S. P. Lee, A. J. McMichael, J.-W. Gratama, et al.
T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFN{gamma} production
Int. Immunol.,
April 1, 2006;
18(4):
591 - 601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Westwood, M. J. Smyth, M. W. L. Teng, M. Moeller, J. A. Trapani, A. M. Scott, F. E. Smyth, G. A. Cartwright, B. E. Power, D. Honemann, et al.
Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice
PNAS,
December 27, 2005;
102(52):
19051 - 19056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. L. Teng, M. H. Kershaw, Y. Hayakawa, L. Cerutti, S. M. Jane, P. K. Darcy, and M. J. Smyth
T Cells Gene-engineered with DAP12 Mediate Effector Function in an NKG2D-dependent and Major Histocompatibility Complex-independent Manner
J. Biol. Chem.,
November 18, 2005;
280(46):
38235 - 38241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Moeller, N. M. Haynes, M. H. Kershaw, J. T. Jackson, M. W. L. Teng, S. E. Street, L. Cerutti, S. M. Jane, J. A. Trapani, M. J. Smyth, et al.
Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection
Blood,
November 1, 2005;
106(9):
2995 - 3003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. P.F. Gade, W. Hassen, E. Santos, G. Gunset, A. Saudemont, M. C. Gong, R. Brentjens, X.-S. Zhong, M. Stephan, J. Stefanski, et al.
Targeted Elimination of Prostate Cancer by Genetically Directed Human T Lymphocytes
Cancer Res.,
October 1, 2005;
65(19):
9080 - 9088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
R. A. Willemsen, C. Ronteltap, P. Chames, R. Debets, and R. L. H. Bolhuis
T Cell Retargeting with MHC Class I-Restricted Antibodies: The CD28 Costimulatory Domain Enhances Antigen-Specific Cytotoxicity and Cytokine Production
J. Immunol.,
June 15, 2005;
174(12):
7853 - 7858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Kershaw, J. T. Jackson, N. M. Haynes, M. W. L. Teng, M. Moeller, Y. Hayakawa, S. E. Street, R. Cameron, J. E. Tanner, J. A. Trapani, et al.
Gene-Engineered T Cells as a Superior Adjuvant Therapy for Metastatic Cancer
J. Immunol.,
August 1, 2004;
173(3):
2143 - 2150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Finney, A. N. Akbar, and A. D. G. Lawson
Activation of Resting Human Primary T Cells with Chimeric Receptors: Costimulation from CD28, Inducible Costimulator, CD134, and CD137 in Series with Signals from the TCR{zeta} Chain
J. Immunol.,
January 1, 2004;
172(1):
104 - 113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
