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The target complex consisting of FITC-labeled adapter molecules bound to the AML antigens CD33, CD123, and CLL-1 is a central component of a modular, switchable chimeric antigen receptor (CAR) T-cell platform designed for the treatment of acute myeloid leukemia (AML). In this system, universal CAR-T cells are engineered to recognize the non-human fluorescein isothiocyanate (FITC) tag rather than the tumor antigens directly. The specificity and activity of the CAR-T cells are mediated by bispecific adapter molecules (targeting modules) that bridge the T cells to the leukemia cells by binding to FITC on one end and to CD33, CD123, or CLL-1 on the other [1, 16]. This multi-antigen targeting strategy is specifically designed to overcome the high degree of inter- and intra-patient heterogeneity in AML, which often leads to antigen escape and relapse in single-target therapies [3, 5]. By utilizing a cocktail of adapters, the system can target the broad blast population as well as leukemic stem cells more effectively. Furthermore, the short pharmacokinetic half-life of the adapter molecules allows for precise control over the intensity and duration of the immune response, providing a safety switch to mitigate severe toxicities such as prolonged myelosuppression [4, 9].
The anti-FITC CAR-T cells recognize the FITC (fluorescein isothiocyanate) moiety on the adapter molecules, which are simultaneously bound to the AML-associated antigens CD33, CD123, or CLL-1, thereby bridging the T cell to the tumor cell and triggering activation, cytokine release, and tumor cell lysis [1, 15, 17].
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