CD123 redirected multiple virus-specific T cells for acute myeloid leukemia

Area of Science:

• Immunotherapy
• Hematologic Oncology
• Virology

Background:

• Hematopoietic stem cell transplantation (HSCT) is a curative option for acute myeloid leukemia (AML), but high relapse rates (30-70%) and viral infections (EBV, Adv, CMV) pose significant risks.
• Current treatments include chimeric antigen receptor (CAR)-based T cells for AML and virus-specific cytotoxic T cells (VST) for viral infections.

Purpose of the Study:

• To develop a novel T cell therapy capable of simultaneously targeting AML relapse and viral infections post-HSCT.
• To engineer virus-specific T cells (VST) to express a CAR targeting the AML-associated antigen CD123, creating CD123-CAR-VST.

Main Methods:

• Generated VST from donor PBMCs using dendritic cells pulsed with Epstein-Barr virus (EBV), adenovirus (Adv), and cytomegalovirus (CMV) peptides.
• Transduced VST with a retroviral vector encoding CD123-CAR to create CD123-CAR-VST.
• Assessed CD123-CAR-VST recognition of viral epitopes and specificity against CD123-positive AML cell lines (MOLM13, THP-1) in vitro.

Main Results:

• CD123-CAR-VST successfully recognized EBV, Adv, and CMV epitopes.
• Demonstrated HLA-restricted, virus-specific cytotoxic effector function against EBV-infected targets.
• Confirmed retained specificity against CD123-positive AML cell lines in vitro.

Conclusions:

• CD123-CAR-VST exhibits dual functionality, targeting both viral infections and AML relapse.
• This dual-targeting approach holds potential as a valuable therapeutic strategy for AML patients undergoing HSCT.