CAR-T cell therapy has exhibited many promising preclinical results, however it is also associated with several severe adverse effects. Conditional CAR-T cells are able to reduce or even eliminate these effects dramatically. They will not be activated unless the presences of an additional signal in addition to recognition of targets by CARs. The second signal can be a small molecule to fulfill the circuit of CARs. Alternatively, conditional CAR can integrate an adaptor-specific receptor with affinity for subsequently administered secondary antibodies directed to specific antigen on target cells. The conditional CARs need the administration of an exogenous molecule. Additionaly, absence of exogenous activator molecule does not necessarily lead to the death of CAR-T cell. It works as a switch to turn on the activity of CAR-T cell, which allows more accurate regulation of the efficacy of CAR-T cells and thus improve safety. Creative Biolabs provides advanced construction services for conditional CARs.
The conditional CAR-T cell therapy with small-molecule-dependent signalling has been evaluated in preclinical animal models. For instance, conditional CAR with optimized switches specific for CD19 has been shown to control the activity, tissue-homing, cytokine release, and phenotype of a peptide-specific switchable CAR-T cell in a dose-titratable manner in a Nalm-6 xenograft rodent model of B-cell leukemia. The conditional CAR-T cell dosing regimen could be tuned to provide comparable efficacy to the corresponding conventional anti-CD19 CAR-T cell, but with an alleviated cytokine release syndrome in future clinical application. Another conditional CAR targeting system based on synthetic Notch receptors has recently been described, which enables conditional activation of CAR-T cell upon engagement with a tissue-specific ligand.
Conditional chimeric antigen receptor models and concepts
Nature Reviews Cancer. 2016
CAR-T cell therapy has been rapidly developing in recent years. As a leading biotech company in immunotherapy development, Creative Biolabs now provides conditional CAR construction service. We work with our clients to develop novel CAR-T cell therapy to fight against cancer with improved safety.
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