Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers.
Fiche publication
Date publication
mai 2024
Journal
Cell death & disease
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CALLIER Patrick, Dr GARRIDO Carmen, Dr COLLIN Bertrand, Dr PAIS DE BARROS Jean-Paul, Dr VEGRAN Frédérique, Dr QUERE Ronan, Dr BELLAYE Pierre-Simon, Pr BEDUNEAU Arnaud
Tous les auteurs :
Georgievski A, Bellaye PS, Tournier B, Choubley H, Pais de Barros JP, Herbst M, Béduneau A, Callier P, Collin B, Végran F, Ballerini P, Garrido C, Quéré R
Lien Pubmed
Résumé
We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. Being lipophilic, valrubicin readily incorporated Val-lLs that were loaded with specific antibodies. Val-ILs injected intravenously rapidly reached the bone marrow and spleen, indicating their potential to effectively target cancer cells in these areas. Following the transplantation of human pediatric B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), or acute myeloid leukemia (AML) in immunodeficient NSG mice, we generated patient-derived xenograft (PDX) models, which were treated with Val-ILs loaded with antibodies to target CD19, CD7 or CD33. Only a small amount of valrubicin incorporated into Val-ILs was needed to induce leukemia cell death in vivo, suggesting that this approach could be used to efficiently treat acute leukemia cells. We also demonstrated that Val-ILs could reduce the risk of contamination of CD34 hematopoietic stem cells by acute leukemia cells during autologous peripheral blood stem cell transplantation, which is a significant advantage for clinical applications. Using EL4 lymphoma cells on immunocompetent C57BL/6 mice, we also highlighted the potential of Val-ILs to target immunosuppressive cell populations in the spleen, which could be valuable in impairing cancer cell expansion, particularly in lymphoma cases. The most efficient Val-ILs were found to be those loaded with CD11b or CD223 antibodies, which, respectively, target the myeloid-derived suppressor cells (MDSC) or the lymphocyte-activation gene 3 (LAG-3 or CD223) on T4 lymphocytes. This study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.
Mots clés
Animals, Humans, Liposomes, Mice, Xenograft Model Antitumor Assays, Cell Death, drug effects, Hematologic Neoplasms, drug therapy, Leukemia, Myeloid, Acute, drug therapy, Cell Line, Tumor, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, drug therapy
Référence
Cell Death Dis. 2024 05 11;15(5):328