Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia

Nair, Ramya; Salinas-Illarena, Alejandro; Sponheimer, Monika; Wullkopf, Inès; Schreiber, Yannick; Côrte-Real, João Vasco; del Pozo Ben, Augusto; Marterer, Helena; Thomas, Dominique; Geisslinger, Gerd; Cinatl, Jindrich; Subklewe, Marion; Baldauf, Hanna-Mari (2024): Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia. Clinical and Experimental Medicine, 24 (1): 155. ISSN 1591-9528

Abstract

Knowledge of the molecular pathogenesis of acute myeloid leukemia has advanced in recent years. Despite novel treatment options, acute myeloid leukemia remains a survival challenge for elderly patients. We have recently shown that the triphosphohydrolase SAMHD1 is one of the factors determining resistance to Ara-C treatment. Here, we designed and tested novel and simpler virus-like particles incorporating the lentiviral protein Vpx to efficiently and transiently degrade SAMHD1 and increase the efficacy of Ara-C treatment. The addition of minute amounts of lentiviral Rev protein during production enhanced the generation of virus-like particles. In addition, we found that our 2nd generation of virus-like particles efficiently targeted and degraded SAMHD1 in AML cell lines with high levels of SAMHD1, thereby increasing Ara-CTP levels and response to Ara-C treatment. Primary AML blasts were generally less responsive to VLP treatment. In summary, we have been able to generate novel and simpler virus-like particles that can efficiently deliver Vpx to target cells.

• Dokumententyp: Artikel (LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 452881907
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892