|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4263-4273
Vaccines With Interleukin-12-Transduced Acute Myeloid Leukemia Cells
Elicit Very Potent Therapeutic and Long-Lasting Protective Immunity
Kyriaki Dunussi-Joannopoulos,
Kathlene Runyon,
Jamie Erickson,
Robert G. Schaub,
Robert G. Hawley, and
John P. Leonard
From the Department of Preclinical Research and Development, Genetics
Institute, Andover, MA; and the Hematopoiesis Department, Holland
Laboratory, American Red Cross, Rockville, MD.
Interleukin-12 (IL-12) is a heterodimeric cytokine mediating a
dynamic interplay between T cells and antigen-presenting cells (APCs).
Preclinical studies have demonstrated that recombinant murine IL-12
(rmIL-12) promotes specific antitumor immunity mediated by T cells in
several types of tumors. However, the in vivo antitumor properties of
IL-12 in acute myeloid leukemia (AML) have not been previously
reported. We show here in a murine AML model that systemic administration of rmIL-12 significantly delays tumor growth but is
incapable of rescuing mice from lethal leukemia. In contrast, AML cells
genetically modified to express IL-12 (IL12-AML) using murine stem cell
virus (MSCV) p40 + p35 elicit very potent antileukemic activity.
Vaccines with lethally irradiated IL12-AML cells protect naive mice
against challenge with wild-type AML cells and, more importantly, can cure mice bearing a considerable leukemic burden. Immunized mice show no signs of systemic IL-12 toxicity and their spleen histology is comparable with naive mice spleen. In vivo depletion of IL-12, interferon- (IFN-), or CD8+ T
cells after injections with live IL12-AML cells abrogates completely the antileukemia immune responses. Studies on the in vitro effects of
IFN- on AML cells demonstrate enhanced expression of major histocompatibility complex (MHC) and accessory molecules
and induction of the costimulatory molecules B7.1 and B7.2, but no
significant direct antiproliferative effect. 51Cr release
assays show that rejection of live IL12-AML cells supports the
development of long-lasting leukemia-specific cytotoxic T lymphocyte
(CTL) activity. In conclusion, our results demonstrate that IL12-AML vaccination is a safe and potent immunotherapeutic approach that has a great potential to eliminate minimal residual disease in patients with AML.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
X.-T. Ma, B. Xu, L.-L. An, C.-Y. Dong, Y.-M. Lin, Y. Shi, and K.-F. Wu
Vaccine with {beta}-Defensin 2-Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses
Cancer Res.,
January 15, 2006;
66(2):
1169 - 1176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Liu, J. Idoyaga, A. Charalambous, S.-i. Fujii, A. Bonito, J. Mordoh, R. Wainstok, X.-F. Bai, Y. Liu, and R. M. Steinman
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells
J. Exp. Med.,
December 5, 2005;
202(11):
1507 - 1516.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kozar, R. Kaminski, T. Switaj, T. Oldak, E. Machaj, P. J. Wysocki, A. Mackiewicz, W. Lasek, M. Jakobisiak, and J. Golab
Interleukin 12-based Immunotherapy Improves the Antitumor Effectiveness of a Low-Dose 5-Aza-2'-Deoxycitidine Treatment in L1210 Leukemia and B16F10 Melanoma Models in Mice
Clin. Cancer Res.,
August 1, 2003;
9(8):
3124 - 3133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bello-Fernandez, J. Stasakova, A. Renner, N. Carballido-Perrig, M. Koening, M. Waclavicek, O. Madjic, L. Oehler, O. Haas, J. M. Carballido, et al.
Retrovirus-mediated IL-7 expression in leukemic dendritic cells generated from primary acute myelogenous leukemias enhances their functional properties
Blood,
March 15, 2003;
101(6):
2184 - 2190.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Curti, M. Parenza, and M. P. Colombo
Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma
Blood,
January 15, 2003;
101(2):
568 - 575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-J. Kim, R. R. Brutkiewicz, and H. E. Broxmeyer
Role of 4-1BB (CD137) in the functional activation of cord blood CD28-CD8+ T cells
Blood,
October 16, 2002;
100(9):
3253 - 3260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Dunussi-Joannopoulos, K. Zuberek, K. Runyon, R. G. Hawley, A. Wong, J. Erickson, S. Herrmann, and J. P. Leonard
Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses
Blood,
August 13, 2002;
100(5):
1551 - 1558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Gruber, D. C. Skelton, and D. B. Kohn
Requirement for NK Cells in CD40 Ligand-Mediated Rejection of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Cells
J. Immunol.,
January 1, 2002;
168(1):
73 - 80.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Deng and G. Q. Daley
Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia
Blood,
June 1, 2001;
97(11):
3491 - 3497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. R. Appelbaum, J. M. Rowe, J. Radich, and J. E. Dick
Acute Myeloid Leukemia
Hematology,
January 1, 2001;
2001(1):
62 - 86.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
