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DOI: 10.1055/s-0036-1582502
Engineered precursor T cells from human umbilical cord blood using an alpharetroviral vector platform
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.