Our goal is to revolutionize cancer therapy on a global basis by developing TCR T-cell therapies (called SPEAR T-cells) with the potential to treat a wide range of cancer types and patients.
Our TCR T-cell therapies have advantages over other immune therapies and cancer therapies. The video below provides more information.
The immune system plays an important role in targeting and destroying diseased and abnormal cells.
There are two modes of action by which the body's immune system can target and destroy diseased or abnormal cells.
The HLA peptide complex presents peptides that are derived from intracellular target proteins. TCRs target and bind to a specific HLA peptide complex, resulting in the targeting and destruction of the relevant cell.
Unfortunately binding of naturally occurring T-cell receptors to cancer targets tend to be very poor because cancer proteins appear very similar to naturally occurring proteins and are very good at evading the immune system. T-cell receptors that recognize "self-proteins" are eliminated during early human development.
At Adaptimmune, we harness the immune system and use engineered T-cell receptors to fight back against cancer. The affinity enhanced T-cell receptors, unlike their natural counterparts, can recognize and bind to cancer cells and as a result, can stimulate the immune system to target and destroy cancer cells.
Naturally occurring T-cell receptors struggle to recognize cancer proteins. This is because the cancer proteins appear very similar to other proteins within the body, "self-proteins". At Adaptimmune, we have a unique ability to engineer the affinity of the T-cell receptors so that they can recognize cancer proteins and as a result can detect and fight cancer within patients.
T-cell receptors consist of two associated protein chains: the alpha (α) and beta (β) chains. Each of the chains has two regions: a variable region and a constant region. The constant region sits next to the T-cell membrane and the variable region of the two chains binds to the target peptides. The variable region of each TCR chain has three hypervariable complementarity determining regions or CDRs. Our technology modifies these CDRs in order to enhance affinity to the cancer cell's HLA peptide complex.
By engineering the sequences that encode the T-cell receptors within a T-cell we can generate a T-cell therapy which works with a patient's own immune system to target specific cancer peptides. Our technology platform allows us to identify and select the T-cell receptors which are likely to prove the most effective in patients whilst minimizing off-target (non-cancer cell) binding.