|
|
Blood, 15 February 2006, Vol. 107, No. 4, pp. 1332-1341.
Prepublished online as a Blood First Edition Paper on October 25, 2005; DOI 10.1182/blood-2005-03-1259.
 Previous Article | Next Article 
Submitted March 29, 2005
Accepted September 28, 2005
Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation
Raphael F Rousseau*, Ettore Biagi, Aurelie Dutour, Eric S Yvon, Michael P Brown, Tiffany Lin, Mei Zhuyong, Bambi Grilley, Edwina Popek, Helen E Heslop, Adrian P Gee, Robert A Krance, Uday Popat, George Carrun, Judith F Margolin, and Malcolm K Brenner
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA; Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA; The Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA
* Corresponding author; email: rfrousse{at}txccc.org.
CD40L generates immune responses in leukemia-bearing mice, an effect that is potentiated by IL-2. We studied the feasibility, safety and immunologic efficacy of an IL-2- and CD40L-expressing recipient-derived tumor vaccine consisting of leukemic blasts admixed with skin fibroblasts transduced with adenoviral vectors encoding hIL-2 and hCD40L. Ten patients (including 7 children) with high-risk acute myeloid (n=4) or lymphoblastic (n=6) leukemia in cytologic remission (after allogeneic stem cell transplantation n=9 or chemotherapy alone n=1) received up to six subcutaneous injections of the IL2/CD40L vaccine. None of the patients were receiving immunosuppressive drugs. No severe adverse reactions were noted. Immunization produced a 10- to 890-fold increase in the frequencies of MHC-restricted T cells reactive against recipient-derived blasts. These leukemia-reactive T cells included both Tc/Th1 and Th2 subclasses, as determined from their production of granzyme-B, interferon- and interleukin-5. Two patients produced systemic IgG antibodies that bound to their blasts. Eight patients remained disease-free for 27-62 months after treatment (5-year overall survival, 90%). Thus, even in heavily treated patients, including recipients of allogeneic stem cell transplants, recipient-derived antileukemia vaccines can induce immune responses reactive against leukemic blasts. This approach may be worthy of further study, particularly in patients with a high risk of relapse.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. E. Seif, D. M. Barrett, M. Milone, V. I. Brown, S. A. Grupp, and G. S. D. Reid
Long-term protection from syngeneic acute lymphoblastic leukemia by CpG ODN-mediated stimulation of innate and adaptive immune responses
Blood,
September 17, 2009;
114(12):
2459 - 2466.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. T. Ho, M. Vanneman, H. Kim, T. Sasada, Y. J. Kang, M. Pasek, C. Cutler, J. Koreth, E. Alyea, S. Sarantopoulos, et al.
Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation
PNAS,
September 15, 2009;
106(37):
15825 - 15830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Nienhuis
Development of gene therapy for blood disorders
Blood,
May 1, 2008;
111(9):
4431 - 4444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H. Vonderheide
Prospect of Targeting the CD40 Pathway for Cancer Therapy
Clin. Cancer Res.,
February 15, 2007;
13(4):
1083 - 1088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
