Preferred Label : C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs;
NCIt definition : Autologous CD34-positive, hematopoietic stem progenitor cells (HSPCs) genetically
modified with a lentiviral vector expressing short hairpin RNA that targets human
chemokine receptor 5 (CCR5) mRNA (shCCR5), the HIV entry inhibitor C46, a membrane-anchored
46-amino acid sequence found in HIV-1 gp41, and the drug resistance gene P140K, a
mutant form of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT),
used to potentially provide resistance against human immunodeficiency virus (HIV)
infection. Human autologous CD34 HSPCs are isolated and transduced ex vivo with the
pRSC-H1.shCCR5.Ubic.C46.EF1alpha.P140K.wpre lentiviral vector. shCCR5 binds to CCR5
mRNA and inhibits the expression of CCR5, a HIV-1 co-receptor that mediates HIV attachment
and cell entry. Additionally, the expression of C46 blocks HIV-1 fusion to the cellular
membrane. Upon re-infusion into the HIV-infected lymphoma patient, the C46/shCCR5/P140K
lentiviral vector-transduced autologous HSPCs are resistant to HIV entry, which protects
these cells against HIV infection and replication, and increases the amount of HIV-resistant
CD4 T-cells. HIV-resistant HSPCs could provide long-term protection against latent
HIV infection and against HIV-associated cancers. In addition, the formation of immune
cells resistant to HIV may result in the destruction of HIV-infected cells. P140K
expression facilitates the in vivo chemoselection of gene-modified HSPCs, using O6-benzylguanine
(O6BG)/bis-chloroethylnitrosourea (BCNU/carmustine), which increases the proportion
of these HIV resistant CD34 cells. P140K also protects these stem cells from future
destruction by certain chemotherapeutic agents; if cancer were to develop, P140K is
not inactivated by the MGMT inhibitor O6BG.;
Origin ID : C119735;
UMLS CUI : C3899843;
Semantic type(s)
- Cell [UMLS semantic type]
- concept_is_in_subset
- has_target
