γδ T Cell Therapy Development for Ovarian Cancer

γδ T cells are distributed throughout the body, helping to detect and eliminate cancer early. At present, γδ T cells is showing extraordinary potential in the research of immunotherapy for ovarian cancer (OC).

Introduction to OC

Ovarian cancer (OC) is a devastating disease, largely because patients will not develop symptoms before the disease progresses. More than 70% of patients are in advanced clinical stage (III / IV) at the time of the first diagnosis. OC is a chemosensitive tumor. The surgical resection followed by platinum-based chemotherapy can produce objective remission in some cases. In addition, even after successful surgical treatment, more than 70% of patients will relapse, and the 5-year survival rate is less than 40%. Therefore, it is essential to develop a new form of treatment for the disease. Immunotherapy is a promising treatment for many solid tumors including OC. However, the ability of tumor cells to establish immunosuppressive microenvironment to evade immune surveillance is a major obstacle to tumor immunotherapy. Therefore, it is very important to understand the role of immunosuppressive microenvironment in OC.

γδ T Cell in OC Development

γδ T cells have a dual role in OC development.

• γδ T cells as foes in OC development

On the one hand, γδ T cells can kill cancer cells through antibody dependent cellular cytotoxicity (ADCC). ADCC occurs when CD16 (FcγR III) is present on γδ T cells. CD16 binds to the Fc region of IgGs, which is another γδ T cell target recognition method besides TRAIL and FasL. Binding to target cells may trigger cytotoxicity or other effector functions (for example, IFN-γ secretion). The researchers cloned the extracellular domain of Vγ9 Vδ2 T cell receptor (TCR) from tumor infiltrating lymphocyte (TIL) in OC and combined it with the Fc domain of human IgG1. This chimeric antibody mediates cell killing through ADCC in a dose-dependent manner. In vivo, this TCR Vγ9 Vδ2-Fc significantly inhibits cancer cell growth and improves survival rate in a human OC xenograft model.

• γδ T cells as friends in OC development

On the other hand, γδ T17 cells are the main source of IL-17 and play an immunosuppressive effect in tumors. γδ T17 cells secrete IL-17, which induces the production of vascular endothelial growth factor and other angiogenesis-related factors. Studies have shown that the OC microenvironment may mobilize and recruit γδ T cells, which secrete large amounts of inflammatory cytokine IL-17A, which reduces cytotoxicity, enhances immunosuppressive activity, establishes an effective immunosuppressive microenvironment, and promotes tumor progression and immune escape.

γδ T cells may be a prognostic factor of OC, providing a good target for immunotherapy, making it possible to optimize immunotherapy.

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

What Can We Do?

The unique biological characteristics of γδ T cells make them an attractive source of unmodified cell-based adoptive immunotherapy, and they can also be used for gene manipulation. Whether as carriers of chimeric antigen receptors (CATs) or TCR derived from αβ T cells, γδ T cells can combine tissue resident biology and innate target recognition with antigen-specific activation and selection. In addition, a better understanding of the interaction between γδ T cells and tumor molecules, as well as their regulation and activation in normal tissues and tumors, can be performed by targeted or checkpoint therapy.

Based on these, Creative Biolabs proposes research services for the development of γδ T cell therapy for cancer, including γδ TCRs Services, γδ T cell development services, γδ T cell engineering services and so on, to assist the immunotherapy of OC. If you want to get more information, please feel free to contact us.

Reference

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