The present invention relates to lipid nanoparticle loaded with antitumoral agent and
functionnalized to target immosuppressive cells. Inventors developpe valrubicin-loaded
immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analogue
of daunorubicin. Being lipophilic, valrubicin readily incorporated Val-lLs that were loaded with
specific antibodies.. 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. Inventors 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, they 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
lymphocyteactivation 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.