DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies

Le Pogam, Carole ; Patel, Satyananda ; Gorombei, Petra ; Guerenne, Laura ; Krief, Patricia ; Omidvar, Nader ; Tekin, Nilgun ; Bernasconi, Elena ; Sicre, Flore ; Schlageter, Marie-Helene ; Chopin, Martine ; Noguera, Maria-Elena ; West, Robert ; Abu, Ansu ; Mathews, Vikram ; Pla, Marika ; Fenaux, Pierre ; Chomienne, Christine ; Padua, Rose Ann (2015) DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies Oncotarget, 6 (32). pp. 32494-32498. ISSN 1949-2553

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Official URL: http://www.oncotarget.com/index.php?journal=oncota...

Related URL: http://dx.doi.org/10.18632/oncotarget.5572


We have previously shown that a specific promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) DNA vaccine combined with all-trans retinoic acid (ATRA) increases the number of long term survivors with enhanced immune responses in a mouse model of acute promyelocytic leukemia (APL). This study reports the efficacy of a non-specific DNA vaccine, pVAX14Flipper (pVAX14), in both APL and high risk myelodysplastic syndrome (HR-MDS) models. PVAX14 is comprised of novel immunogenic DNA sequences inserted into the pVAX1 therapeutic plasmid. APL mice treated with pVAX14 combined with ATRA had increased survival comparable to that obtained with a specific PML-RARA vaccine. Moreover, the survival advantage correlated with decreased PML-RARA transcript levels and increase in anti-RARA antibody production. In HR-MDS mice, pVAX14 significantly improved survival and reduced biomarkers of leukemic transformation such as phosphorylated mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1. In both preclinical models, pVAX14 vaccine significantly increased interferon gamma (IFNγ) production, memory T-cells (memT), reduced the number of colony forming units (CFU) and increased expression of the adapter molecule signalling to NF-κB, MyD88. These results demonstrate the adjuvant properties of pVAX14 providing thus new approaches to improve clinical outcome in two different models of myeloid malignancies, which may have potential for a broader applicability in other cancers.

Item Type:Article
Source:Copyright of this article belongs to Impact Journals, LLC.
Keywords:Plasmid DNA Based Immunotherapy; MDS; APL; Memory T-cells; Immunology and Microbiology Section; Immune Response; Immunity
ID Code:113914
Deposited On:07 Jun 2018 11:33
Last Modified:07 Jun 2018 12:22

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