γδ T Cells and Adoptive Immunotherapy

Immunotherapy and δ T Cells

The adoptive immunotherapy is accomplished by expanding immune effector cells in vitro and transferring the activated immune cells into the hosts, that target against tumor cells or stimulate an immune response to eliminate tumor cells. It was recently reported that γδ T cells are attractive mediators of cancer immunotherapy. They recognize their targets independently of major histocompatibility complex (MHC)-mediated antigen presentation. γδ T cells have the capacity of secreting abundant cytokines. They exert potent cytotoxicity against a wide range of malignancies. Therefore, γδ T cells have become attractive effector cells for cancer immunotherapy.

Fig.1 Pro- and antitumor effect of γδ T cells. (Raverdeau, 2019)

Principle of Adoptive Immunotherapy with Vγ2Vδ2 T Cells

Adoptive immunotherapy with Vγ2Vδ2 T cells is a potential therapy for a variety of cancers. Stimulation of Vγ2Vδ2 T cells is not dependent on peptides presented by MHC proteins and is, therefore, MHC-unrestricted. Vγ2Vδ2 T cells respond to the presence of small isoprenoid metabolites, such as self isopentenyl pyrophosphate (IPP) or foreign microbial (E)-4-hydroxy-3-methyl but-2-enyl pyrophosphate (HMBPP), in a process requiring the butyrophilin 3A1 (BTN3A1) protein, an immunoglobulin superfamily protein present on all normal and tumor cells. The isoprenoid metabolites bind to the B30.2 intracellular domains of BTN3A1, which alters the cell through an unknown process to allow the Vγ2Vδ2 TCR17 to recognize this intracellular binding.

Antitumor Activity of γδ T Cells and GPC3-Specific CTLs in Vivo

Scientists performed adoptive cell transfer of expanded cells in a mouse model. We subcutaneously inoculated SK-Hep-1/vec or SK-Hep-1/hGPC3 cell lines into NOD/SCID mice and intravenously injected effector cells twice. As effector cells, they used CD8+ or CD8- cells that were isolated from cultured cells using CD8 microbeads at day 14, and we used all cells that included both CD8+ and CD8- cells. As shown, the growth of SK-Hep-1/hGPC3 treated with CD8+or CD8- cells was significantly inhibited compared with the negative control. Also, treatment of all cells, including both CD8+ and CD8-cells, tended to show an additive inhibitory effect. On the other hand, the growth of SK-Hep-1/vec that was inhibited in the treatment of CD8-or all cells was not inhibited by the treatment of CD8+ cells. These results indicate that cultured cells had antitumor effects due to the respective CD8+ and CD8- cells.

Clinical Application of γδ T Cells in Adoptive Immunotherapy

Table.1 γδ T cells anti-tumor effect in clinical studies. (Zou, 2016)

Our Services

We have a variety of services, including but not limited to the following aspects:

• γδ T cell development services to promote the advance of different diseases’ therapy
• γδ TCR generation and repertoires analysis services
• γδ T cell engineering services to increase their efficacy in cancer immunotherapy

Why Us?

• Trustworthy: our company focuses on γδ T cell therapy development services, involving hundreds of businesses.
• Optional: you can choose a set of solutions or combination schemes according to your needs, and our experts will provide you with a variety of possibilities.
• Efficient: the scientists in our team are very dedicated, and they will deliver the results for the first time.

Current therapeutic options for cancer treatment have made advancements in recent years and the survival rate of patients with cancer has gradually improved. However, these therapies remain far from satisfactory in most cancers. Creative Biolabs meets your needs in any γδ T cell development project, which is one of the attractive areas in developing novel anti-tumor therapeutics. If you have any questions, please contact us.

References

1. Raverdeau, M.; et al. γδ T cells in cancer: a small population of lymphocytes with big implications. Clinical & Translational Immunology. 2019, 8(10).
2. Yoshikawa, T.; et al. Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy. International Journal of Oncology. 2014.
3. Zou, C.; et al. γδ T cells in cancer immunotherapy. Oncotarget. 2016, 8(5):8900.