A New Paradigm for T cell Therapy in Solid Tumor Treatment
Addressing barriers to solid tumor treatment with Tmod™ T cells, designed to kill tumor cells while sparing normal cells
Current cellular immunotherapies work by binding to and killing tumor cells that overexpress “tumor-specific” antigens. The challenge with this approach is that most of these antigens are not truly tumor-specific and are also expressed on normal cells. Thus, most cancer therapies result in on-target, off-tumor killing of normal cells, ultimately leading to unacceptable toxicities.
Safeguarding normal cells widens the therapeutic window to access unexploited targets & targets previously constrained by toxicity
The Tmod™ mechanism utilizes two receptors to exploit gene losses in tumors that demarcate tumor from normal cells
We invented a precision-targeting cellular system – the Tmod™ mechanism – that incorporates two receptors, an activator and a blocker to aim the powerful armaments of immune cells directly at tumors.
The activator recognizes antigens on tumor cells that trigger their killing, while the blocker recognizes antigens on normal cells that protect them from destruction.
Exploiting the loss of genes in tumor cells, known as loss of heterozygosity (LOH), provides an opportunity to unequivocally differentiate tumors from normal tissues.
Our approach exploits a common and irreversible loss of genetic material unique to tumor cells, called LOH. LOH occurs when a cell that is originally heterozygous at a gene locus loses one of its two parental alleles at that locus. This happens frequently in tumor cells and can be identified in cancer patients by using next generation sequencing technology.
Our Tmod™ platform exploits LOH in tumor cells. The activator and blocker on the Tmod™ T cell are designed to signal based on the presence and absence of antigens displayed on the cell surface. The activator recognizes antigens which are present on both tumor and normal cells, and binds to initiate killing. On the normal cell however, the blocker recognizes the antigen expressed by the presence of both alleles (no LOH) and turns off the activator’s killing, sparing the normal cells. See Hamburger et al. paper
The Tmod™ platform is robustly different from other cell therapy systems
Our blocker technology enables precise, personalized and effective T cell targeting. The blocker component equips Tmod™ cells with the capacity to exploit common gene losses in tumors that mark them as distinct from normal cells. Integration of two signals in this fashion exploits the machinery evolved by immune cells, placing us one step ahead of cancer.