Core Viewpoint - The article discusses the advancements in CAR-T cell therapy, particularly focusing on enhancing its efficacy against low-antigen expressing cancers through the integration of intrinsically disordered regions (IDR) with CAR molecules [2][4][6]. Group 1: CAR-T Cell Therapy Overview - CAR-T cells have shown unprecedented success in treating hematological malignancies and are being explored for various diseases, including cancers, infections, autoimmune diseases, and fibrosis [2]. - A significant limitation of CAR-T therapy is its low sensitivity to antigens, requiring hundreds of antigen molecules for activation, which restricts its application to cancers with high antigen expression [2][3]. Group 2: Research Findings - A study published by a team from Yale University demonstrated that fusing IDR with CAR molecules enhances the cytotoxicity of CAR-T cells against low-antigen cancers by promoting biomolecular condensation [4][6]. - The research involved constructing CAR-IDR fusion proteins targeting CD19, CD22, and HER2, which improved the binding of CAR-T cells to cancer cell targets and increased the release of cytotoxic factors [6][8]. Group 3: Implications of IDR Integration - The integration of IDR into CAR-T cells resulted in better anti-tumor effects in both hematological and solid tumor models without spontaneous activation in the absence of antigens, indicating a novel mechanism of action [8]. - This approach expands the toolkit for CAR engineering, suggesting that IDR can serve as a new modular element to enhance the anti-tumor efficacy of CAR-T cells [8].