γδ T cells represent a new generation of universal immune cell therapy.
The current engineered autologous alpha beta (αβ) T cell products have shown efficacy in hematological malignancies; however, comparable efficacy in solid tumors is yet to be proven. The cell platform and novel targeting approaches Adicet is developing are aimed at harnessing the tumor specific immunity of γδ T cells. We believe that γδ T cells have a superior potential than αβ T cells to be active in solid tumors.
Advantage of γδ T cells
The unique features of these cells combine adaptive (γδ TCR-mediated) and innate (NK-cell like) immunity to specifically recognize and eliminate tumor cells while sparing normal, healthy cells. Unlike αβ T cells, γδ T cells perform their tumor killing function in a MHC-independent manner and thus can be used in an allogeneic setting without the risk of causing Graft vs Host Disease (GvHD). Additionally, γδ T cells perform their immune surveillance by naturally homing to various tissues giving them a superior potential to αβ T cells to eradicate solid tumors in tissues. The cytotoxicity and anti-tumor activity of γδ T cells has been demonstrated in vitro and in vivo in mouse models.
To date, the use of these cells has been limited because γδ T cells represent only a small fraction of the peripheral blood mononuclear cells (1-5%). Adicet has developed a proprietary and robust method to activate and expand different subsets of γδ T cells to numbers sufficient for utilization in the clinical setting.
Adicet* is engineering γδ T cells with chimeric antigen receptors (CARs) and T cell receptors (TCRs) directed to disease-specific cell surface and intracellular targets in order to enable the precise engagement and killing of tumor cells. Adicet intends to generate multiple clinical product candidates for various hematological and solid tumor cancers.
*In collaboration with Regeneron
Unique ability to generate T Cell Receptor-Like monoclonal antibodies (TCRLs) directed to the intracellular proteome
To complement its immune cell platform, Adicet Bio has proven capabilities to target the intracellular proteome by generating and validating high affinity and high specificity T Cell Receptor-Like monoclonal antibodies (TCRLs). These TCRLs are directed to disease specific antigens presented on the cell surface by the MHC Class I complexes. In addition, Adicet also established Epitarget™, a proprietary technology, to identify and validate novel disease-specific peptide targets.
These TCRLs can be used 1) to arm γδ T cells; 2) as T cell engager (bispecific) or 3) as Antibody Drug Conjugates (ADC).
Proprietary Cell Platform Process
Adicet has developed a proprietary cell platform process to activate, engineer, and expand γδ T cells. The process allows for generation of cell banks that can be used to treat many patients.