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  • Acquired Diseases
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Gene transfer of GM-CSF, CD80 and CD154 cDNA enhances survival in a murine model of acute leukemia with persistence of a minimal residual disease

Gene Therapy volume 7, pages 1312–1316 (2000)Cite this article

Abstract

Gene transfer of various cytokines and co-stimulatory molecules has been reported to induce a potent antileukemic immunity in murine models, however, the relative efficiency and possible synergistic effects between candidate genes have not been extensively investigated. We analyzed in a murine model of BCR/ABL acute leukemia whether gene transfer of CD154, CD80 or GM-CSF as a single agent or combination of CD154 + GM-CSF, CD80 + CD154 and GM-CSF + CD80 in leukemic cells could enhance survival. We observed that CD154 gene transfer induced a marked inhibition of leukemogenicity, and also that CD154 and combination of GM-CSF and CD80 gene transfer protected mice against subsequent challenge with leukemic cells and had a therapeutic effect for a pre-established leukemia disease. We also found minimal residual leukemic disease by RT-PCR for 6 to 12 months in 0 to 25% of animals injected with transduced leukemic cells and surviving the challenge without evidence of disease, except in the control empty plasmid group where very few mice survived the challenge but all of those were positive by RT-PCR. These findings suggest that leukemic cell vaccination by gene transfer can induce a tumor dormancy phenomenon compatible with long-term survival.

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Acknowledgements

This work was upported by the Ligue Contre le Cancer (Comité du Nord and Comité du Pas de Calais), the Association de Recherche sur le Cancer, the Association Recherche Transfusion, the Fondation contre la Leucémie, and the GEFLUC.

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Authors and Affiliations

  1. Unité INSERM 524, IRCL, Lille, France

    R Vereecque, G Buffenoir, D Hetuin & B Quesnel

  2. Laboratoire d'Hématologie, CHU Lille, Lille, France

    C Preudhomme

  3. Service des Maladies du Sang, CHU Lille, Lille, France

    F Bauters, P Fenaux & B Quesnel

Authors
  1. R Vereecque
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  2. G Buffenoir
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  3. C Preudhomme
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  7. B Quesnel
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Vereecque, R., Buffenoir, G., Preudhomme, C. et al. Gene transfer of GM-CSF, CD80 and CD154 cDNA enhances survival in a murine model of acute leukemia with persistence of a minimal residual disease. Gene Ther 7, 1312–1316 (2000). https://doi.org/10.1038/sj.gt.3301228

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