TCR-Engineered T Cells Eradicate Multiple Solid Tumors Targeting β-Catenin Mutation

Recent advances in immunotherapy research have focused on enhancing the efficacy of adoptive cell therapies against cancers, particularly in challenging contexts such as solid tumors and acute myeloid leukemia (AML). A novel genome-wide CRISPR screening platform, PreCiSE, has been developed to identify key genetic regulators that improve natural killer (NK) cell persistence, cytotoxicity, and resistance to immunosuppressive tumor microenvironments, providing insights for next-generation CAR-NK therapies. Concurrently, research on tumor-specific mutations such as CTNNB1S37F has elucidated how mutated peptides are naturally processed and presented via common HLA class I molecules, highlighting potential targets for precision immunotherapies across multiple cancer types including endometrial, non-small cell lung, and prostate cancers. Additionally, studies on immune synapse formation revealed the essential role of the CD99 molecule in T cell antigen-presenting cell conjugate formation and actin reorganization, which are critical steps for effective T cell activation. In AML and other cancers, innovative approaches including TCR-like CARs and bispecific antibodies are being developed to overcome the difficulty of identifying tumor-specific targets without harming normal hematopoietic cells, with stress-induced molecules like B7H6 presenting promising therapeutic targets. Collectively, these findings underscore a multifaceted strategy to improve adoptive cellular immunotherapy by combining genetic screening, molecular targeting of tumor-specific mutations, and enhancing immune cell functionality.