Allogeneic double-negative T-cell therapy for acute myeloid leukemia
Enoch Tin1, Jongbok Lee2, Li Zhang3
1Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Current Opinion in Pharmacology
|May 29, 2025
Summary
Double-negative T cells (DNTs) show strong anti-acute myeloid leukemia (AML) activity and do not cause graft-versus-host disease. These cells are promising for off-the-shelf AML cellular therapy.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- CD3+CD4-CD8- double-negative T cells (DNTs) are a unique T cell subset.
- DNTs exhibit potent cytotoxicity against acute myeloid leukemia (AML).
Purpose of the Study:
- To evaluate the therapeutic potential of allogeneic DNTs for AML treatment.
- To explore DNTs as a basis for off-the-shelf cellular therapy.
Main Methods:
- Review of existing clinical trial data and scientific literature on DNTs in AML.
- Analysis of DNT characteristics, including cytotoxicity, allogeneic compatibility, and CAR-transduction potential.
Main Results:
- Allogeneic DNTs do not induce graft-versus-host disease.
- DNTs show promising efficacy in early-stage clinical trials for AML.
- DNTs can be engineered with CARs and synergize with conventional AML treatments.
- Persistent CAR+ T cells in long-term AML remission patients predominantly exhibit a DNT phenotype.
Conclusions:
- Allogeneic DNTs possess unique therapeutic properties for AML.
- DNTs are a strong candidate for off-the-shelf adoptive cellular therapy for AML.
