PMID- 33473357 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210122 IS - 2329-0501 (Print) IS - 2329-0501 (Electronic) IS - 2329-0501 (Linking) VI - 20 DP - 2021 Mar 12 TI - Evaluation of the human type 3 adenoviral dodecahedron as a vector to target acute myeloid leukemia. PG - 181-190 LID - 10.1016/j.omtm.2020.11.009 [doi] AB - Intensive systemic chemotherapy is the gold standard of acute myeloid leukemia (AML) treatment and is associated with considerable off-target toxicities. Safer and targeted delivery systems are thus urgently needed. In this study, we evaluated a virus-like particle derived from the human type 3 adenovirus, called the adenoviral dodecahedron (Dd) to target AML cells. The vectorization of leukemic cells was proved very effective at nanomolar concentrations in a time- and dose-dependent manner, without vector toxicity. The internalization involved clathrin-mediated energy-dependent endocytosis and strongly correlated with the expression of alpha(V)beta(3) integrin. The treatment of healthy donor peripheral blood mononuclear cells showed a preferential targeting of monocytes compared to lymphocytes and granulocytes. Similarly, monocytes but also AML blasts were the best-vectorized populations in patients while acute lymphoid leukemia blasts were less efficiently targeted. Importantly, AML leukemic stem cells (LSCs) could be addressed. Finally, Dd reached peripheral monocytes and bone marrow hematopoietic stem and progenitor cells following intravenous injection in mice, without excessive spreading in other organs. These findings reveal Dd as a promising myeloid vector especially for therapeutic purposes in AML blasts, LSCs, and progenitor cells. CI - (c) 2020 The Authors. FAU - Caulier, Benjamin AU - Caulier B AD - University Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France. AD - Institute of Biology and Pathology, Laboratory of Cellular Hematology, University Grenoble Alpes Hospital, Grenoble, France. AD - Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, University Grenoble Alpes, Grenoble, France. FAU - Stofleth, Gaelle AU - Stofleth G AD - Institute of Biology and Pathology, Laboratory of Cellular Hematology, University Grenoble Alpes Hospital, Grenoble, France. AD - Department of Pediatric Onco-Immuno-Hematology, University Grenoble Alpes Hospital, Grenoble, France. FAU - Hannani, Dalil AU - Hannani D AD - University Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France. FAU - Guidetti, Melanie AU - Guidetti M AD - Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, University Grenoble Alpes, Grenoble, France. FAU - Josserand, Veronique AU - Josserand V AD - Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, University Grenoble Alpes, Grenoble, France. FAU - Laurin, David AU - Laurin D AD - Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, University Grenoble Alpes, Grenoble, France. AD - Etablissement Francais du Sang Auvergne Rhone-Alpes, Grenoble, France. FAU - Chroboczek, Jadwiga AU - Chroboczek J AD - University Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France. FAU - Mossuz, Pascal AU - Mossuz P AD - Institute of Biology and Pathology, Laboratory of Cellular Hematology, University Grenoble Alpes Hospital, Grenoble, France. AD - Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, University Grenoble Alpes, Grenoble, France. FAU - Plantaz, Dominique AU - Plantaz D AD - Department of Pediatric Onco-Immuno-Hematology, University Grenoble Alpes Hospital, Grenoble, France. LA - eng PT - Journal Article DEP - 20201117 PL - United States TA - Mol Ther Methods Clin Dev JT - Molecular therapy. Methods & clinical development JID - 101624857 PMC - PMC7797482 OTO - NOTNLM OT - acute myeloid leukemia OT - adenoviral dodecahedron OT - delivery vector OT - leukemic stem cells OT - virus-like particles COIS- The authors declare no competing interests. EDAT- 2021/01/22 06:00 MHDA- 2021/01/22 06:01 PMCR- 2020/11/17 CRDT- 2021/01/21 05:34 PHST- 2020/06/10 00:00 [received] PHST- 2020/11/10 00:00 [accepted] PHST- 2021/01/21 05:34 [entrez] PHST- 2021/01/22 06:00 [pubmed] PHST- 2021/01/22 06:01 [medline] PHST- 2020/11/17 00:00 [pmc-release] AID - S2329-0501(20)30236-9 [pii] AID - 10.1016/j.omtm.2020.11.009 [doi] PST - epublish SO - Mol Ther Methods Clin Dev. 2020 Nov 17;20:181-190. doi: 10.1016/j.omtm.2020.11.009. eCollection 2021 Mar 12.