|
|
Blood, 15 March 2005, Vol. 105, No. 6, pp. 2436-2442.
Prepublished online as a Blood First Edition Paper on November 9, 2004; DOI 10.1182/blood-2004-07-2556.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor–reactive cytotoxic T lymphocytes
Ettore Biagi,
Gianpietro Dotti,
Eric Yvon,
Edward Lee,
Martin Pule,
Stephane Vigouroux,
Stephen Gottschalk,
Uday Popat,
Raphael Rousseau, and
Malcolm Brenner
From the Center for Cell and Gene Therapy, Baylor College of Medicine, Methodist Hospital and Texas Children's Hospital, Houston.
Clinical benefits from monoclonal antibody therapy for B-chronic lymphocytic leukemia (B-CLL) have increased interest in developing additional immunotherapies for the disease. CD40 ligand is an accessory signal for T-cell activation and can overcome T-cell anergy. The OX40-OX40 ligand pathway is involved in the subsequent expansion of memory antigen-specific T cells. We expressed both CD40L and OX40L on B-CLL cells by exploiting the phenomenon of molecular transfer from fibroblasts overexpressing these ligands. We analyzed the effects of the modified B-CLL cells on the number, phenotype, and cytotoxic function of autologous T cells in 7 B-CLL patients. Transfer of CD40L and OX40L was observed in all and was followed by the up-regulation of B7-1 and B7-2. The culture of CD40L/OX40L-expressing B-CLL cells with autologous T cells generated CD4+/CD8+ cytotoxic T-cell lines, which secreted interferon- (IFN-) and granzyme-B/perforin in response to autologous, but not to allogeneic, B-CLL cells or to autologous T-cell blasts. CD40L or OX40L alone was insufficient to expand tumor-reactive T cells. The combination of CD40L and OX40L on B-CLL cells may allow the generation of therapeutic immune responses to B-CLL, either by active immunization with modified tumor cells or by adoptive immunotherapy with tumor-reactive autologous T cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Murata, B. H. Ladle, P. S. Kim, E. R. Lutz, M. E. Wolpoe, S. E. Ivie, H. M. Smith, T. D. Armstrong, L. A. Emens, E. M. Jaffee, et al.
OX40 Costimulation Synergizes with GM-CSF Whole-Cell Vaccination to Overcome Established CD8+ T Cell Tolerance to an Endogenous Tumor Antigen
J. Immunol.,
January 15, 2006;
176(2):
974 - 983.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Serghides, J. Bukczynski, T. Wen, C. Wang, J.-P. Routy, M.-R. Boulassel, R.-P. Sekaly, M. Ostrowski, N. F. Bernard, and T. H. Watts
Evaluation of OX40 Ligand as a Costimulator of Human Antiviral Memory CD8 T Cell Responses: Comparison with B7.1 and 4-1BBL
J. Immunol.,
November 15, 2005;
175(10):
6368 - 6377.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Palena, K. A. Foon, D. Panicali, A. G. Yafal, J. Chinsangaram, J. W. Hodge, J. Schlom, and K. Y. Tsang
Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules
Blood,
November 15, 2005;
106(10):
3515 - 3523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Biagi, R. Rousseau, E. Yvon, M. Schwartz, G. Dotti, A. Foster, D. Havlik-Cooper, B. Grilley, A. Gee, K. Baker, et al.
Responses to Human CD40 Ligand/Human Interleukin-2 Autologous Cell Vaccine in Patients with B-Cell Chronic Lymphocytic Leukemia
Clin. Cancer Res.,
October 1, 2005;
11(19):
6916 - 6923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zhou, Y. Tagaya, R. Tolouei-Semnani, J. Schlom, and H. Sabzevari
Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4+ T cells in the absence of APCs
Blood,
April 15, 2005;
105(8):
3238 - 3246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
