Anti-fluorescein chimeric antigen receptor (Anti-FITC CAR)

The Anti-fluorescein chimeric antigen receptor (Anti-FITC CAR) is a synthetic, engineered receptor designed to provide a modular and controllable approach to CAR-T cell therapy. Unlike traditional CARs that are fixed to a single tumor-associated antigen, the Anti-FITC CAR is engineered to recognize fluorescein isothiocyanate (FITC), a small-molecule hapten not naturally found in the human body (Tamada et al., 2012, Clin Cancer Res). This system functions as a universal platform where the CAR-T cells are redirected to specific cancer cells through the administration of FITC-labeled adapter molecules, such as antibodies or small-molecule ligands (Ma et al., 2016, PNAS). By adjusting the dose or type of these adapter molecules, clinicians can potentially control the intensity of the immune response and target multiple different antigens sequentially or simultaneously to prevent antigen escape (Lee et al., 2019, Mol Ther). This modularity aims to overcome the severe toxicities often associated with conventional CAR-T therapies, such as cytokine release syndrome, by allowing for the 'switching off' of T-cell activity upon cessation of adapter administration. The technology is currently being explored in various clinical and preclinical settings for both hematologic and solid malignancies.

Other names

Anti-FITC CARFluorescein-specific chimeric antigen receptorFITC-directed CARAnti-fluorescein isothiocyanate chimeric antigen receptorUniversal CAR (uCAR)

The Anti-FITC CAR-T cell acts as a universal platform that does not bind directly to endogenous antigens; instead, it recognizes fluorescein isothiocyanate (FITC) conjugated to adapter molecules (bispecific switches). These adapters bridge the CAR-T cell to specific tumor-associated antigens, triggering CAR clustering, T-cell signaling (via CD3-zeta and co-stimulatory domains like 4-1BB or CD28), and subsequent granzyme/perforin-mediated lysis of the target cell (Ma et al., 2016, PNAS; Tamada et al., 2012, Clin Cancer Res).