Background: Alpharetroviral vectors may reduce the risk of insertional mutagenesis.
Methods: Cord blood-derived CD34+ cells were transduced and differentiated into preTs in vitro. Two promoter-envelope combinations were comparatively assessed. A chimeric antigen
receptor (CAR) against CD123 along with the inducible suicide gene iCaspase 9 were
used as genes of interest.
Results: The sarcoma virus-derived promoter with a modified feline endogenous retrovirus envelope
glycoprotein yielded in superior transduction and expression rates. Transgene positive
cells did neither show proliferative impairment nor alteration in differentiation.
The sarcoma virus-derived promoter only expressed sufficient levels of iCaspase 9
for dimerizer-induced apoptosis. The CD123 CAR was efficiently expressed and proved
to be functional.
Conclusion: Alpharetroviral vectors represent a potentially safer approach for stem cell-based
immunotherapies for cancer.
