%0 Journal Article
%T Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia.
%A Nair R
%A Salinas-Illarena A
%A Sponheimer M
%A Wullkopf I
%A Schreiber Y
%A Côrte-Real JV
%A Del Pozo Ben A
%A Marterer H
%A Thomas D
%A Geisslinger G
%A Cinatl J
%A Subklewe M
%A Baldauf HM
%J Clin Exp Med
%V 24
%N 1
%D 2024 Jul 13
%M 39003408
%F 5.057
%R 10.1007/s10238-024-01425-w
%X 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.