{Reference Type}: Journal Article
{Title}: Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia.
{Author}: Nair R;Salinas-Illarena A;Sponheimer M;Wullkopf I;Schreiber Y;Côrte-Real JV;Del Pozo Ben A;Marterer H;Thomas D;Geisslinger G;Cinatl J;Subklewe M;Baldauf HM;
{Journal}: Clin Exp Med
{Volume}: 24
{Issue}: 1
{Year}: 2024 Jul 13
{Factor}: 5.057
{DOI}: 10.1007/s10238-024-01425-w
{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.