nalotimagene carmaleucel

Nalotimagene carmaleucel (Zalmoxis) is a cell-based gene therapy developed to aid immune reconstitution in adult patients with high-risk hematological malignancies undergoing haploidentical hematopoietic stem cell transplantation (HSCT). The therapy consists of allogeneic T lymphocytes from the same donor as the stem cells, which have been genetically modified using a retroviral vector to express a suicide gene: the Herpes Simplex Virus Thymidine Kinase (HSV-TK). It also expresses a truncated human low-affinity nerve growth factor receptor (ΔLNGFR) as a selection marker. The primary clinical advantage is that the HSV-TK gene acts as a pharmacological safety switch; if the patient develops severe graft-versus-host disease (GvHD), the administration of ganciclovir or valganciclovir results in the selective elimination of the transduced T cells, as the HSV-TK enzyme converts these prodrugs into toxic metabolites that induce apoptosis. Although it received conditional marketing authorization in Europe in 2016, the authorization was withdrawn in 2019 by the developer for commercial reasons.

Brand names

Zalmoxis

Other names

HSV-TK transduced donor lymphocytesTK-cellsHSV-TK gene-modified T-cells