Klin Padiatr 2016; 228 - A25
DOI: 10.1055/s-0036-1582502

Engineered precursor T cells from human umbilical cord blood using an alpharetroviral vector platform

J Hübner 1, SS Hoseini 1, JD Suerth 2, D Hoffmann 2, M Maluski 1, J Herbst 1, B Eiz-Vesper 3, M Heuser 4, A Schambach 2, MG Sauer 1
  • 1Pediatric Hematology/Oncology
  • 2Experimental Hematology
  • 3Transfusion Medicine
  • 4Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany

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.