At the end of 2019, Medigen obtained exclusive authorization from Medinet Co. Ltd in Japan for Gamma-delta T (γδT/GDT cells) cell therapy technology, and completed the technology transfer in early 2020, and will conduct this technology in clinical trials (special control methods) as well as develop their applications in Taiwan.

Medinet is a listed biotechnology company in Japan that specializes in the production of various stem cells and immune cells. In addition to accepting the commissioned services of OEM production, it also develops their γδT cells for several clinical trials and applies them for cell therapy currently in Japan. Medigen has successfully transferred the in vitro expansion technology of γδT cells from Medinet, which were used in clinical trials.

Generally, the T cell receptors (TCRs) of T cells composed of α-chains and β-chains, so they are called αβT cells. Another group of T cells with a smaller number (approximately accounting for the surrounding blood About 1-5% of T cells), their TCR is composed of γ-chain and δ-chain, so they are called γδ T cells. γδT cells are mainly distributed in the intestinal mucosa, skin and other mucosal tissues. They not only participate in many immune responses but also play a role in immune regulation, such as inflammation and can kill cancer cells by directly identification. The γδ T cells are recognized as a member of innate immunity, since they response to antigen quickly and are not restricted by HLA molecules (MHC restriction). Later, it was discovered that γδ T cells can activate T cells and B cells in the adaptive immunity system by secreting various factors, sometimes, they also exhibit memory-type immune responses. These are the characteristics of adaptive immune responses. Therefore, most researchers now agree that γδT cells have both the characteristics and functions of innate immune response as well as adoptive immune response, and are one of the important cells that perform communication and bridging between these two major immune responses. In addition, γδT cells can regulate the immune system by secreting TNF-α, IFN-γ and IL-17, and can also play a role similar to dendritic cells by presenting tumor antigens to αβT cells (activating αβT cells’ anti-cancer function ) and B cells (promoting Isotype-switching of B cells). The functions of γδT cells in innate immunity are very similar to those of natural killer (NK) cells. Not only do they express various typical NK receptors on the cell surface, such as NKG2D, but also exhibit cytotoxic effects on stress-induced damage cells, mutated cells, virus infected cells and cancer cells.

The mechanism of cancer cells recognition and killing of γδ T cell is very similar to that of NK cells. γδ T cells expressed NKG2D, NCR, CD16, DNAM-1 (activating receptor) and death ligand, which are commonly found on NK cells, it can also use its own unique TCR (γδ) to distinguish normal cells from cancer cells, and then selectively kill cancer cells.

Early studies have found that the TCR of γδ T cells can identify non-peptide phosphoantigens (pAg), such as IPP (Isopentenyl pyrophosphate). The isopentenyl pyrophosphate is a by-product in the process of synthesizing cholesterol of normal cells. The content of IPP in normal cells is not rich, however, due to the increased energy demand in many tumor cells, the altered metabolic response makes IPP accumulate on cancer cells. Therefore, γδT cells can selectively kill cancer cells by this mechanism.

The use of adoptive T cell therapy to treat cancer has been in the field of medical science for nearly 30 years. In the past, most T cell therapies were based on αβ T cells, however, in recent years, adoptive immune cells therapies based on γδ T cells have been increasing. This is mainly due to the following factors:

1. The αβT cell therapy often causes cytokine storm, while the γδT cells are less concerned.
2. The specific αβT cells need a tumor-specific antigen (TSA) or tumor-associated antigen (TAA) on cancer cells to exert their anticancer activities, however, it may not be able to find the TSA or TAA on most cancer cells. In contrast, the γδT cells can distinguish cancer cells without TSA or TAA.
3. Tumor cells are capable of escaping the cytotoxicity of αβT cells by impairing the expression HLA-I molecules or downregulating the expression of HLA-I molecules, whereas the antitumor activity of γδT cells is not affected by HLA-I expression.