From the Guidelines
Gamma delta T cells represent a promising therapeutic approach for acute myeloid leukemia (AML), with potential advantages over conventional T cell therapies, including reduced risk of graft-versus-host disease and innate ability to recognize stress-induced ligands on AML cells. The use of gamma delta T cells in AML treatment is an area of ongoing research, with various approaches being explored, including adoptive cell transfer and CAR-modification to target AML-specific antigens such as CD33 or CD123 1. Aminobisphosphonates like zoledronic acid can be used to stimulate gamma delta T cells, often in combination with low-dose IL-2. However, the microenvironment of AML can suppress gamma delta T cell function, highlighting the potential need for combination therapies with immune checkpoint inhibitors to enhance efficacy.
Key aspects of gamma delta T cell therapy in AML include:
- Adoptive cell transfer, where gamma delta T cells are isolated, expanded ex vivo, and reinfused into patients
- CAR-modification to target AML-specific antigens
- Stimulation with aminobisphosphonates like zoledronic acid, often combined with low-dose IL-2
- Potential combination with immune checkpoint inhibitors to overcome suppressive effects of the AML microenvironment.
Given the current state of research, gamma delta T cell therapy should be considered an experimental approach for AML treatment, with further clinical validation required before it can become a standard treatment option. As research continues to evolve, guidelines such as those outlined in the NCCN guidelines insights: acute myeloid leukemia, version 2.2021, will play a crucial role in integrating new therapies, including gamma delta T cell treatments, into clinical practice 1.
From the Research
Gamma Delta T Cells in Acute Myeloid Leukemia (AML)
- Gamma delta T cells play a crucial role in disease control in AML and have become an area of therapeutic interest 2.
- These cells can recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface.
- AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, leading to γδ T cell-mediated cytotoxicity.
Therapeutic Strategies and Clinical Trials
- Clinical trials leveraging γδ T cell biology have used unmodified and modified allogeneic cells as well as bispecific engagers and monoclonal antibodies 2.
- Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of relapse, enhanced graft-versus-leukemia effect, and decreased graft-versus-host disease in patients with AML who have higher reconstitution of γδ T cells following allogeneic hematopoietic stem cell transplantation.
- Other therapeutic strategies for AML include targeted agents, such as CDK9 inhibitors, which have shown promise in clinical trials 3.
Diagnosis and Treatment of AML
- Diagnosis of AML is based on the presence of immature leukemia cells in the blood, and/or bone marrow or less often in extra-medullary tissues 4.
- Treatment options for AML include conventional chemotherapy, targeted agents, and hematopoietic stem cell transplantation (HSCT) 5, 4, 6.
- HSCT has become the main treatment for AML, with allo-SCT showing better OS and DFS benefits than auto-SCT, but auto-SCT is associated with lower TRM 6.