Strengthening the immune response to cancer
Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of B-cell malignancies. The estrogen receptor-binding fragment associated antigen 9 (EBAG9) inhibits the release of cytolytic enzymes from cytotoxic T lymphocytes. Micro-RNA-mediated EBAG9 downregulation in transplanted CTLs from immunized mice improved their cytolytic competence in a tumor model. A single-step retrovirus transduction process links CAR or TCR expression with miRNA-mediated EBAG9 downregulation. Despite higher cytolytic efficacy, the release of cytokines associated with cytokine release syndrome remains unaffected. Collectively, EBAG9-silencing enhances the effector capacity of TCR- and CAR-engineered T cells resulting in improved tumor eradication facilitating efficient manufacturing, and decreasing the therapeutic dose.

Source: 10.1016/j.ymthe.2022.07.009