With the help of these cells, it should one day be possible to treat a variety of different types of cancer. In addition to the different types of blood cancer, the therapy of solid tumours should also benefit from this. The basis has already been proven in preclinical studies. A phase 1 clinical trial is planned for 2024 to investigate the treatment of leukaemia and lymphoma using these cells.1
The γδ T cells represent a special class of unconventional T cells. They express somatically rearranged γ and δ chains of the T cell receptor (TCR). In a previous study, they were used in a mouse model in the fight against cancer cells (glioblastoma multiforma).2 The stereotactic use of allogeneic human γδ T cells led to a reduction in tumours. We know that they were also successfully used in a mouse model to combat influenza A viruses. The γδ T cells analysed in the current study were derived from human umbilical cord blood and have a very diverse TCRγδ repertoire. They have a unique subtype composition that differs from that of foetal and adult peripheral blood cells.3
Preclinical models have shown that γδ T cells have a strong cytotoxicity against various types of cancer cells. They were even effective against leukaemic cells that were resistant to previous chemotherapy. Leukaemia patients who had previously received allogeneic bone marrow transplants with αβ-T cells were also able to benefit from these cells.
Some reports suggest that reconstitution of donor γδ T cells could improve disease-free survival in these patients. This led to a growing interest in these special cells. Ex vivo, cytotoxic activity of the isolated γδTIL against autologous tumour cells was observed.3
The Singapore research group has expanded umbilical cord-derived γδ T cells (CBγδ) in vitro in an irradiated, Epstein-Barr virus-transformed feeder cell-based modified rapid expansion protocol. Using single-cell RNA sequencing, the research group was able to observe the progressive differentiation of naive CBγδ cells. These expressed neoantigen-reactive tumour-infiltrating lymphocyte-like as well as tissue-resident memory precursor-like and antigen-presenting cell-like gene signatures.
Tracing of TCRγδ clones showed a tendency towards cytotoxic effector differentiation. The CBγδ cultures had a high expansion potential. This was due to their poorly differentiated nature. A large proportion of the expanded CBγδ exhibited a TSCM-like phenotype. This was associated with higher antitumour activity in adaptively transferred CD8+ T cells.3
T cells derived from umbilical cord blood have enormous potential in the fight against tumour cells. They are more adaptable than adult T cells and can take on additional functions. CBγδ T cells are currently a great source of hope in tumour research. We are eagerly awaiting the data from the planned phase 1 trial.1