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Letter. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia

Letter. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia
Letter. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia
Despite improved molecular characterization of malignancies and development of targeted therapies, acute leukemia is not curable and few patients survive more than 10 years after diagnosis. Recently, combinations of different therapeutic strategies (based on mechanisms of apoptosis, differentiation and cytotoxicity) have significantly increased survival. To further improve outcome, we studied the potential efficacy of boosting the patient's immune response using specific immunotherapy. In an animal model of acute promyelocytic leukemia, we developed a DNA-based vaccine by fusing the human promyelocytic leukemia?retinoic acid receptor-alpha (PML-RARA) oncogene to tetanus fragment C (FrC) sequences. We show for the first time that a DNA vaccine specifically targeted to an oncoprotein can have a pronounced effect on survival, both alone and when combined with all-trans retinoic acid (ATRA). The survival advantage is concomitant with time-dependent antibody production and an increase in interferon-bold gamma (IFN-bold gamma). We also show that ATRA therapy on its own triggers an immune response in this model. When DNA vaccination and conventional ATRA therapy are combined, they induce protective immune responses against leukemia progression in mice and may provide a new approach to improve clinical outcome in human leukemia.
1078-8956
1413-1417
Padua, Rose Ann
4e1a41c6-9b8a-4aac-b665-5248c79d15ed
Larghero, Jerome
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Robin, Marie
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le Pogam, Carol
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Schlageter, Marie-Helene
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Muszlak, Sacha
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Fric, Jan
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West, Robert
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Rousselot, Philippe
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Phan, T. H.
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Mudde, L.
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Teisserenc, H.
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Carpentier, Antoine F.
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Kogan, Scott
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Degos, Laurent
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Pla, Marika
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Bishop, J. Michael
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Stevenson, Freda
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Charron, Dominique
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Chomienne, Christine
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Padua, Rose Ann
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Larghero, Jerome
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Robin, Marie
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le Pogam, Carol
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Schlageter, Marie-Helene
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Muszlak, Sacha
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Fric, Jan
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West, Robert
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Rousselot, Philippe
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Phan, T. H.
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Mudde, L.
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Teisserenc, H.
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Carpentier, Antoine F.
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Kogan, Scott
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Degos, Laurent
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Pla, Marika
4c36354b-55cd-4ac9-85fc-d0888d8566bb
Bishop, J. Michael
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Stevenson, Freda
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Charron, Dominique
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Chomienne, Christine
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Padua, Rose Ann, Larghero, Jerome, Robin, Marie, le Pogam, Carol, Schlageter, Marie-Helene, Muszlak, Sacha, Fric, Jan, West, Robert, Rousselot, Philippe, Phan, T. H., Mudde, L., Teisserenc, H., Carpentier, Antoine F., Kogan, Scott, Degos, Laurent, Pla, Marika, Bishop, J. Michael, Stevenson, Freda, Charron, Dominique and Chomienne, Christine (2003) Letter. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia. Nature Medicine, 9 (11), 1413-1417. (doi:10.1038/nm949).

Record type: Article

Abstract

Despite improved molecular characterization of malignancies and development of targeted therapies, acute leukemia is not curable and few patients survive more than 10 years after diagnosis. Recently, combinations of different therapeutic strategies (based on mechanisms of apoptosis, differentiation and cytotoxicity) have significantly increased survival. To further improve outcome, we studied the potential efficacy of boosting the patient's immune response using specific immunotherapy. In an animal model of acute promyelocytic leukemia, we developed a DNA-based vaccine by fusing the human promyelocytic leukemia?retinoic acid receptor-alpha (PML-RARA) oncogene to tetanus fragment C (FrC) sequences. We show for the first time that a DNA vaccine specifically targeted to an oncoprotein can have a pronounced effect on survival, both alone and when combined with all-trans retinoic acid (ATRA). The survival advantage is concomitant with time-dependent antibody production and an increase in interferon-bold gamma (IFN-bold gamma). We also show that ATRA therapy on its own triggers an immune response in this model. When DNA vaccination and conventional ATRA therapy are combined, they induce protective immune responses against leukemia progression in mice and may provide a new approach to improve clinical outcome in human leukemia.

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More information

Published date: November 2003

Identifiers

Local EPrints ID: 26510
URI: http://eprints.soton.ac.uk/id/eprint/26510
ISSN: 1078-8956
PURE UUID: e63135b5-338f-42a0-b079-1ab311825ddf
ORCID for Freda Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 19 Apr 2006
Last modified: 16 Mar 2024 02:54

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Contributors

Author: Rose Ann Padua
Author: Jerome Larghero
Author: Marie Robin
Author: Carol le Pogam
Author: Marie-Helene Schlageter
Author: Sacha Muszlak
Author: Jan Fric
Author: Robert West
Author: Philippe Rousselot
Author: T. H. Phan
Author: L. Mudde
Author: H. Teisserenc
Author: Antoine F. Carpentier
Author: Scott Kogan
Author: Laurent Degos
Author: Marika Pla
Author: J. Michael Bishop
Author: Freda Stevenson ORCID iD
Author: Dominique Charron
Author: Christine Chomienne

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