In Vitro and In Vivo Antitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL against CD33+ Acute Myeloid Leukemia

Abstract EN

Genetic engineering of T cells with chimeric T-cell receptors (CARs) is an attractive strategy to treat malignancies.

It extends the range of antigens for adoptive T-cell immunotherapy, and major mechanisms of tumor escape are bypassed.

With this strategy we redirected immune responses towards the CD33 antigen to target acute myeloid leukemia.

To improve in vivo T-cell persistence, we modified human Epstein Barr Virus-(EBV-) specific cytotoxic T cells with an anti-CD33.CAR.

Genetically modified T cells displayed EBV and HLA-unrestricted CD33 bispecificity in vitro.

In addition, though showing a myeloablative activity, they did not irreversibly impair the clonogenic potential of normal CD34+ hematopoietic progenitors.

Moreover, after intravenous administration into CD33+ human acute myeloid leukemia-bearing NOD-SCID mice, anti-CD33-EBV-specific T cells reached the tumor sites exerting antitumor activity in vivo.

In conclusion, targeting CD33 by CAR-modified EBV-specific T cells may provide additional therapeutic benefit to AML patients as compared to conventional chemotherapy or transplantation regimens alone.