SITC 2021 | Mechanism of action of Tmod™ T-cell therapy and pre-clinical evidence

Alexander Kamb, PhD, A2 Biotherapeutics, Agoura Hills, CA, describes the mechanism of action of the Tmod™ (T-cell module) platform and comments on in vitro and in vivo data evaluating this new T-cell therapy. The mechanism of discrimination between normal and tumor cells is dependent on two functions: an activating receptor that recognizes an antigen on the surface of normal and tumor cells and an inhibitory (or blocker) receptor recognizing an antigen lost from the tumor cell and present on all normal cells. This system is activated only when the blocker signal is absent, leading to selective killing of tumor cells. A range of activator receptors recognizing solid tumor antigens such as mesothelin (MSLN) and carcinoembryonic antigen (CEA) can be paired with different blocker receptors such as the HLA-A*02-targeted blocker. Data from in vitro experiments has shown that engineered Tmod™ cells are highly robust, modular, and sensitive as they are effective across multiple targets, can distinguish between tumor and normal cells in mixed cell cultures, and are sensitive over a range of antigen levels. In addition, data from xenograft models further demonstrated that the Tmod™ platform was able to kill tumor cells selectively. It is now essential to evaluate this system in humans to ensure that it can differentiate normal from tumor cells. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.