Chimeric antigen receptor (CAR) T cells promote the destruction of cancer cells by recognizing target antigens using an antibody fragment that they’ve been engineered to express. Trouble is, not all antibody fragments (scFvs) employed in CARs are equally suited for such uses, and even well characterized and highly selective antibodies that are presumed ideal can fail when repurposed and put to the tumor-targeting test. In a January paper in Scientific Reports, Ludwig Lausanne’s Steven Dunn and colleagues described a new screening method to select antibody fragments for CARs that are less likely to fail such tests. The in vitro CAR library discovery approach links antibody-driven bridging of tumor and effector T cells with an informative and functionally relevant CAR activation reporter signal. This establishes early on that the selected antibody isn’t just recognizing its intended target, but that it is doing so in a manner that can trigger CAR-T cell function. Steven and his colleagues validated their methods by isolating novel scFvs that recognize the cancer antigen mesothelin. The results show that their functional screening method can enrich and identify antibody fragments well suited for use in CAR-T cells, including many that would have been missed by classical in vitro antibody screening technologies.
This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).