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Thans to their unique ability to recognise cancer cells and viruses the Gamma Delta (γδ) T cells, are a unique subset of T cells, and they present a promising avenue in immunotherapies and development of new cancer treatment. With this in mind, our supplier BPS bioscience has developed a whole range of innovative products, for the development of new therapeutic solutions based on (γδ) T cells.
In the T lymphocytes family, alpha beta (αβ) T and gamma delta (γδ) T cells, can be distinguished by the expression of either αβ or γδ TCR (T cell receptor), respectively. Less common than the αβ T cells, γδ T cells can recognize and kill viruses and cancer cells without the need for antigen presentation via Major Histocompatibility Complex (MHC) molecules. Instead, γδ TCRs recognize antigens in a similar way as antibodies, being able to recognize full protein antigens. This makes them highly versatile and effective in targeting a wide range of tumors.
Considered to bridge the innate and adaptive immune systems, activated γδ T-cells display strong cytotoxic activity through the release of granzyme B and perforin. They also produce IFNγ or TNFα to amplify the immune response, thereby counteracting tumor development. Although γδ T-cells make up only a small fraction of the cells present in PBMC, it was found that this small population is actually quite potent in killing viruses and cancer cells.
In humans, γδ TCRs, αβ TCRs, and antibodies result from gene rearrangements and offer the immune system the possibility to recognize several different types of antigens. γδ T-cells express a combination of either of 7 different Vγ TCR chains (Vγ2, 3, 4, 5, 8, 9, and 11), paired with either of 4 Vδ (Vδ1, 2, 3, and 5) chains (Fig.1).
Novel γδ T-cell-based immunotherapies are being developed that primarily focus on the two major γδ T-cell subtypes that infiltrate tumors (Vδ1 and Vδ2) (Fig.2). The Vδ1 T-cell subset contains both effector T-cells as well as regulatory T-cells with tumor-promoting potential. Vδ1 T-cells are less abundant than Vδ2 T-cells, but this subset is enriched in epithelia and among tumor infiltrating lymphocytes (TILs).
Vδ2 T-cells, in contrast, are found primarily in circulation, making up 1-10% of the total CD3+ T-cell population in healthy individuals. This percentage can rapidly expand upon stimulation. The Vγ9Vδ2 T-cell receptor can sense intracellular phosphorylated metabolites that accumulate in cancer cells as a result of mevalonate pathway dysregulation or upon pharmaceutical intervention. Vγ9Vδ2 T cells are involved mostly in immune responses to pathogens and long-term modulation of inflammation. Vγ9Vδ2 T cells are being studied for the treatment of solid tumors and hematological disorders and are becoming a highly promising cancer therapy.
With many years of experience in developing innovative solutions in the field of Immunology and cancer research, our partner BPS Bioscience have developed a number of tools to study γδ TCRs.
The two new reporter cell lines, have been generated by overexpression of human Vγ9Vδ2 or Vγ4Vδ1 TCR using lentiviral transduction.
The cell lines are ideal for screening for Vγ9Vδ2 or Vγ4Vδ1 TCR agonist antibodies, or for use as a positive control for Vγ9Vδ2/ Vγ4Vδ1 TCR evaluation and optimizing experimental conditions.(Fig. 3).
One issue with studying γδ T cells is the very low abundance of these cells in circulation. In response to researcher’s need to to generate the amount of cells needed, BPS Bioscience have developed a robust Vγ9Vδ2 T Cell Expansion Kit
It allows researchers to successfully activate and expand enough Vγ9Vδ2 cells for γδ T-cell based immunotherapy-related studies.
Another approach to bypass the small population of native Vγ4Vδ1 or Vγ9Vδ2 T cells is to create them by introducing the specific γδ TCR into cells. BPS Biosciences have released the Vγ4Vδ1 TCR Lentivirus and Vγ9Vδ2 TCR Lentivirus, used to develop the reporter cell lines as separate products. These lentiviruses can be used to express either the Vγ4Vδ1 or Vγ9Vδ2 TCR in cells and test the function of this TCR against the target of interest.
Used in combination with the TCR or TCR/B2M Knockout Jurkat cells, it will allow you to generate a reproducible cell model to study the γδ TCRs without the need to have to isolate T cells and expand each time they need to do a study. In order to develop an immortalized reporter cell lines for screening, you can use the δ TCR lentiviruses with our luciferase reporter TCR or TCR/B2M knockout cell lines.
Thanks to our strong collaboration with our partner BPS Bioscience, you have an easy access to a number of innovative products, to develop new γδ TCRs based therapeutical solutions, and open a new therapeutic avenues for cancer and infections.
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