Gamma delta T cells represent a new generation of universal cell therapy
The current engineered autologous alpha beta T cell products have shown significant 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 gamma delta T cells. The Company believes that gamma delta T cells have a superior potential compared to alpha beta T cells to be active in both solid tumors and hematological cancers.
Advantage of gamma delta T cells
Gamma delta T cells have unique attributes that Adicet believes make them especially well-suited to be used for cancer therapy. The unique features of these cells combine adaptive (gamma delta TCR-mediated) and innate (NK-cell like) immunity to specifically recognize and eliminate tumor cells while sparing normal, healthy cells. Unlike alpha beta T cells, gamma delta 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, gamma delta T cells perform their immune surveillance by naturally homing to various tissues giving them a superior potential to alpha beta T cells to eradicate solid tumors in tissues. Adicet has demonstrated the cytotoxicity and anti-tumor activity of gamma delta T cells in vitro and in vivo in mouse models.
To date, the use of these cells has been limited because gamma delta T cells represent only a small fraction of the peripheral blood mononuclear cells (1-5%). Adicet has developed a proprietary and robust process to activate and expand different subsets of gamma delta T cells to numbers sufficient for utilization in the clinical setting.
Novel Targeting Moieties
Adicet is engineering gamma delta T cells with chimeric antigen receptors (CARs) and T cell receptors (TCRs) directed to either tumor-specific cell surface or 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, and other diseases.
Unique ability to generate T Cell Receptor-Like monoclonal antibodies (TCRL’s) directed to the intracellular proteome
To complement its immune cell platform, Adicet has developed a proprietary T cell receptor-like antibody (TCRL) platform technology, a monoclonal antibody technology which enables the generation of CARs that recognize tumor antigens inside tumor cells, also known as intracellular proteins. These intracellular proteins are processed by the cell and presented by antigen-presenting molecules encoded by the major histocompatibility complex, (MHC). The ability to selectively bind to tumor antigens derived specifically from intracellular proteins is a critical advantage to immunocellular therapy due to the scarcity of tumor-specific surface antigens on solid tumors. The Company’s approach to generating CARs for some product candidates takes advantage of this ability.
These TCRLs can be used 1) to arm gamma delta T cells; 2) as T cell engager (bispecific) or 3) as Antibody Drug Conjugates (ADC).