γδ T Cell Therapy Development Services for Tumors and Cancers

γδ T cells are a distinct subgroup of T cells containing T cell receptors (TCRs) γ and TCR δ chains. Compared to αβ T cells, γδ T cells without MHC restriction on tumor antigen recognition have strong cytotoxic effects on tumor cells. γδ T cells have been considered as wonderful effector cells for cancer immunotherapy. Creative Biolabs is an excellent expert in γδ T cell research and γδ T cell based immunotherapy. We provide a series of high-quality services for the development of γδ T cell based immunotherapy.

Roles of γδ T Cells in Cancer Development

γδ T cells are a subgroup of T cells that are structurally and functionally different from conventional αβ T cells, accounting for 0.5-5% of all T-lymphocytes. γδ T cells have been shown a dual effect during cancer progression.

Fig.1 Antitumor and protumor functions of γδ T cells. (Zhao, 2018)

• Antitumor Effect

Specific γδ T cells have been shown to exert an antitumor role in many ways. Firstly, some special γδ T cells such as Vγ9 Vδ2 T cells have been revealed to lyse cancer cells in many types of cancer including breast cancer, renal cancer, and head and neck squamous carcinomas, through the perforin-granzyme pathway. Secondly, γδ T cells have been reported to eliminate cancer cells through the ligands TRAIL and FasL. Thirdly, γδ T cells are able to kill cancer cells through antibody-dependent cellular cytotoxicity (ADCC) via FcγRIII (CD16) expression. Fourthly, some cytokines such as TNF-α, IFN-γ, and IL-17 are released by γδ T cells. These cytokines can inhibit cancer growth by enhancing antitumor immunity and inhibiting cancer angiogenesis. Lastly, γδ T cells can exert their antitumor effect in some indirect ways such as promoting B cell antibody secretion, acting as antigen presenting cells (APCs), triggering dendritic cell (DC) maturation, and inducing robust NK cell-mediated antitumor cytotoxicity.

• Protumor Effect

Some specific γδ T cells have been reported to promote cancer progression, such as γδ T17 cells, Vδ1 T cells, and Vδ1 Treg cells. In various types of cancer such as gallbladder cancer and ovarian cancer, γδ T17 cells can promote cancer progression by promoting angiogenesis. Besides, γδ T cells can weaken the antitumor ability of immunocytes. For example, Vδ1 γδ T cells can suppress DC maturation and their APC functions in human breast tumors. Furthermore, γδ T cells also play a key role in enhancing the function of immunosuppressive cells, which are responsible for converting tumor-induced inflammation into immunosuppression and promoting cancer angiogenesis.

Fig.2 Classification of γδ T cells towards tumors. (Zhao, 2018)

γδ T Cell Based Immunotherapy for Cancer

γδ T cells have emerged as attractive candidates for cell immunotherapy due to their unique antitumor effects. Unmodified γδ T cells can kill tumors via direct antitumor cytotoxicity such as ADCC and strong cytokine production ability. Moreover, modified γδ T cells by genetic engineering strategies also can be used for tumor treatment. For example, γδ T cells engineered to express chimeric antigen receptors (CARs) or αβ T cell-derived TCRs, exert exciting antitumor activities by combining tissue resident characteristics and γδ T cell innate-like recognition with antigen-specific activation and engagement of multiple costimulatory signals.

Vγ9Vδ2 T cells are the most important γδ T cells used for immunotherapy. Several studies showed BrHPP, zoledronate and IL-2 can be applied to maintain the activation status of Vγ9Vδ2 T cells and increase the killing capacity to tumor cells. Besides, some studies also revealed Vγ9Vδ2 T cells expanded ex vivo under the stimulation of zoledronate and IL-2. These cultured γδ T cells were administrated to cancer patients to stimulate anti-tumor responses.

Currently, γδ T cell immunotherapy has been applied for the treatment of a variety of cancer types such as solid cancer and hematological malignancies. Many clinical trials have been completed or are ongoing to evaluate the safety and anti-tumor efficacy of γδ T cells. Although γδ T cell immunotherapy is safe and effective for cancer treatment, there are still many problems required to overcome, such as how to transform the suppressive tumor microenvironment into a normal environment and how to attract more γδ T cells targeting cancer cells.

Our Highlighted Services

Creative Biolabs is a biotechnology company that focuses on the discovery of specific γδ T cells to attack a broad range of human cancers. We have developed and optimized in-house powerful platforms for selective isolation and expansion of antitumor γδ T cell populations from human tissues. Besides, we can use genetic engineering to modify γδ T cells to achieve certain additional features such as targeting specific cancer cells and enhancing antitumor activity. Furthermore, we also provide preclinical validation trials to evaluate the safety and activity of γδ T cell-based cancer immunotherapy.

Features

• Powerful technologies for selective isolation and expansion of antitumor γδ T cells
• A competent and professional team
• Reliable results delivery
• Shorter experiment cycle

If you are interested in our γδ T cell therapy development services, please contact us for more details.

References

1. Zhao, Y.; et al. Gamma-delta (γδ) T cells: friend or foe in cancer development? Journal of Translational Medicine. 2018, 16(1): 3.