[US FDA] The US FDA issued a supplemental approval for Casgevy (exagamglogene autotemcel) for patients aged two years and older with either sickle cell disease with recurrent vaso-occlusive crises or transfusion-dependent β thalassemia.

[Memorial Sloan Kettering Cancer Center] The US FDA has granted full approval for the immunotherapy afamitresgene autoleucel (Tecelra®, also known as afami-cel) for the treatment of patients with  synovial sarcoma.

[Leukemia] Through genome-wide CRISPR/Cas9 screening of CAR-sensitive TP53-wildtype and CAR-resistant TP53-mutated CD19 + B-cell acute lymphoblastic leukemia (B-ALL) cell lines, researchers found the fatty acid transport protein 2 (FATP2) is a leukemia-intrinsic mechanism of CAR-T resistance in TP53-mutant B-ALL.

[Nature Biomedical Engineering] The authors ilustrate the evolving use of cytokines, reveal non-standardized clinical CAR-T cell manufacturing parameters, and summarize preclinical and next-generation concepts, which may improve manufacturing efficiency, cost-effectiveness and therapeutic outcomes.

[Signal Transduction and Targeted Therapy] In vivo engineering technologies that directly deliver CAR genes in situ are emerging as promising approaches to lower costs and simplify manufacturing by bypassing complex ex vivo procedures.

[Leukemia] Investigators confirmed Mucin1-Thomsen-nouvelle (MUC1-Tn) protein expression in T cell acute lymphoblastic leukemia cell lines and primary patient-derived bone marrow cells and subsequently developed MUC1-Tn-targeted CAR T cells.

[Journal for Immunotherapy of Cancer] Scientists found that anti-IL1RAP-CAR-NK cells significantly and specifically enhanced NK cytotoxicity in vitro and decreased tumor growth and lung metastasis in vivo against IL1RAP+ Ewing sarcoma.

[Cancer Immunology Research] The authors evaluated the O-glycosylated IIICS domain of fibronectin as a CAR T cell target.

[ACS Nano] Scientists developed macrophage-preferential ionizable cationic lipid-assisted polymeric nanoparticles to co-deliver mRNAs encoding interferon-γ and a CAR molecule, enabling in vivo engineering of CAR-macrophages with a sustained M1-like phenotype.

[Journal of Experimental Medicine] Investigators identified and validated MUC16 as a clinically relevant target for bladder cancer (BCa), noting enriched expression in tumors recalcitrant to existing therapies. They engineered a second-generation mesothelin-based CAR and demonstrated robust activity across multiple BCa cell lines and patient-derived tumor organoids.

[Cell] Researchers developed 3D DNase-Enhanced Expression Profiling, a deep-tissue spatial transcriptomics approach that reconstructs the four-dimensional dynamics of hair follicle development from a single tissue snapshot.

[Proceedings of the National Academy of Sciences of the United States of America] Scientists showed that chemotactic self-organization governs mammalian hair follicle patterning, explaining how distinct hair patterns emerge across species.