The γδ TCR is an immune receptor expressed by a special type of immune cell with an important role in patrolling the body for any sign of cancer; patients that have this immune cell inside their tumors tend to survival longer (1). The γδ TCR recognizes certain patterns on the surface of cancer cells that signal that it is diseased. These patterns are not present on health cells (2-3).
1. Gentles AJ, et al. 2015. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med, 21: 938-945.
2. Willcox CR, et al. 2020. The distinct MHC-unrestricted immunobiology of innate-like and adaptive-like human γδ T cell subsets-Nature's CAR-T cells. Immunol Rev, 298: 25-46.
3. Payne KK, et al. 2020. BTN3A1 governs antitumor responses by coordinating ab and gd T cells. Science, 369:942-949.
To harness the unique targeting properties of the γδ TCR, Gadeta has developed the TEG platform which equips αβ T cells (used in the production of CAR-Ts) with a defined γδ TCR (4). These patient derived αβ T cells retain their function and proliferative capacity and are ideal ‘carriers’ for the γδ TCR. This new format results in CAR-T potency with broad tumor targeting capabilities of γδ T cell.
4. Marcu-Malina V, et al. 2011. Redirecting αβ T cells against cancer cells by transfer of a broadly tumor-reactive γδT-cell receptor. Blood, 118:50-59.
Advantages of combining attributes of γδ T cells and αβ T cells (TEG) for cell therapy: