Solid tumor-specific Affilin® molecules are currently being evaluated as CAR-T ligands. Specifically, they were confirmed to be functionally expressed on the effector cell surface, mediate target cell-binding and effective target cell-killing in a dose-dependent fashion. Importantly they were just as effective as commonly used antibody fragments.
A prominent advantage of Affilin®-CARs is the seamless affinity adjustments for optimal activity. Being small molecules of just 8kDa each, Affilin® molecules occupy minimal genomic space e.g. for lentiviral packaging. This allows for more freedom and ease of designing even multi-specific CARs to address target-loss or multimeric Affilin® modules for enhanced avidity. Low tonic signaling has been observed with Affilin®-CARs, a drawback commonly observed with scFvs-based CARs. Lastly Affilin® CARs offer alternative IP for antibody fragment-based approaches. Affilin®-CARs therefore present attractive alternatives to the commonly used scFvs-based as CARs.
Chimeric antigen receptor (CAR) T cells can be targeted to a specific protein using an Affilin® as the antigen recognition domain. Affilin® molecules are an excellent choice for designing CARs as they are small, single chain proteins that can be easily engineered into homo/heterodimers for optimal selectivity and affinity to the target cells.