David Chang, Kite Chief Medical Officer told us the idea is to develop compounds that can turn on or off candidate cell therapies based on Cell Design’s molecule ‘dial switches,’ which are small molecules designed to modulate CAR T cell activity.
“The dial switch technology employs small molecule-mediated protein dimerization domains to functionally activate the CAR and, similarly, to “dial-down” the CAR in the absence of the small molecule.
“By incorporating ‘dial switches’ into next generation CAR products, physicians will have the potential to rapidly control and reversibly titrate the activity of CAR T-cells.”
Controlling activity in this way will better target the anti-tumor effects of CAR-T therpies and reduce the occurrence of off-site effects according to Kite.
Dial M for moderate
CDL is not the only firm developing switch technologies cell therapies. However, according to Chang the firm’s approach is more subtle than currently available in which cell activity is controlled by triggering apoptosis.
“CDL has taken the single chain CAR and split it into two proteins. The only way the CAR becomes active is when the two proteins come together, and that can only happen in the presence of the small molecule.
“The ‘dial switch’ breaks from the core disadvantages of the so-called ‘kill switches’ or ‘suicide’ switches in that they can dial back and dial up activity repeatedly, without having to abort the treatment. It is not a last-resort, one-and-done safety-net technology.”
Under the agreement, Kite will receive exclusive worldwide rights to develop and commercialize CAR-T therapies that employ CDL switches.