T Cell Therapy: Rewiring a patient’s immune system to fight cancer
The concept of rewiring a patient’s immune system to fight cancer has been investigated for several decades and has now emerged as the most promising therapeutic approach. Among the various immune-based methods for treating cancer, engineered T cells are proving to be the most potent.
Existing engineered T cell therapies are hampered by recognition, activation and/or signaling issues
While CAR-T approaches have been very effective against hematological malignancies, they have failed to produce good outcomes in solid tumors and are generally hampered by serious/lethal toxicities. These clinical outcomes are likely due to the unnatural signaling provided by the CAR. The unnatural signalling nature of the CAR leads to uncontrolled T cell activation followed by rapid exhaustion in the hostile tumor microenvironment of solid tumors.
TCR approaches enable the T cell to identify select targets and employ natural signaling, which may be preferred in solid tumors, and some clinical activity against solid tumors has been demonstrated. However, TCRs provide limited tumor cell recognition because of its dependency on major histocompatibility complex (MHC) binding, which is frequently absent or downregulated in cancer cells.
TAC provides competitive advantages over CAR and TCR approaches
TAC represents a major advancement to CAR and TCR approaches because TAC (i) enables more selective tumor cell recognition, (ii) activates T cells via the native TCR, leveraging all natural activation and regulatory mechanisms, and (iii) has an absence of tonic signaling and therefore persistence of T memory cells (rather than exhaustion). Consequently, TAC-engineered T cells are expected to induce a controlled, tumor-specific response with reduced toxicities and elimination of solid tumors.
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