UCLA researchers in the Department of Microbiology Immunology and Molecular Genetics have unveiled a novel therapeutic strategy utilizing SSRIs for solid cancer immunotherapy.
BACKGROUND: Immunotherapy has become a highly effective method to combat cancer that enhances a patient’s immune system to attack tumors with high specificity. For instance, immune checkpoint inhibitors (ICI) therapy is a type of cancer immunotherapy that targets immune system components in order to reactivate immune cells to combat tumor cells. Despite the various FDA-approved therapies, a common challenge in ICI therapies is delayed relapses after initial anti-tumor response due to acquired resistance. Many cancer immunotherapies have also demonstrated limited efficacy in solid tumors. Thus, it is vital to identify new targets for immune checkpoint blockade to improve upon existing cancer immunotherapies.
INNOVATION: Researchers at UCLA have uncovered a novel target to activate immune cells. In particular, solid tumor infiltrating cytotoxic CD8 T cells are lucrative targets for immunotherapy. CD8 T cells secrete serotonin, which stimulates further antitumor functions. The serotonin transporter (SERT) negatively regulates this process by depleting serotonin levels in solid tumors. Consequently, researchers tested the use of clinically approved selective serotonin reuptake inhibitors (SSRIs) to inhibit SERT and therefore stimulate T cell antitumor activity in solid tumors. Studies show suppressed tumor growth in various preclinical mouse syngeneic and human xenograft tumor models. SSRI treatment also exhibited significant therapeutic synergy with approved ICI therapies. Researchers have identified SERT as a novel and effective immune checkpoint target and positions SSRIs as promising candidates for next-generation combination cancer therapies.
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DEVELOPMENT-TO-DATE: Efficacy studies completed in preclinical mouse model and human xenograft tumor models