JAML CAR-T cells

JAML CAR-T cells are a novel type of chimeric antigen receptor (CAR) T-cell therapy engineered to target CD19-expressing cells. This therapy incorporates Junction Adhesion Molecule Like (JAML) as an alternative co-stimulatory molecule within the CAR construct, replacing traditional co-stimulatory domains like CD28. JAML contains a PI3K binding motif in its intracellular domain, which is crucial for T cell activation. The primary goal of integrating JAML is to promote the survival and enhance the functional activity of CD8+ CAR-T cells, thereby bolstering anti-tumor immunity. *In vitro* studies have demonstrated that JAML CAR-T cells exhibit comparable manufacturability and cytotoxicity to CD28 CAR-T cells. Notably, they show a higher proportion of juvenile phenotype cells, lower tonic signaling, increased CD8+ T cell proliferation and skewing, and reduced cytokine production. Transcriptomic analysis further revealed an enrichment of cytotoxic genes associated with NK and CD8+ cytotoxic T cells, alongside lower exhaustion signatures, suggesting a potentially improved and sustained anti-tumor response.