Researchers at St. Jude created a chimeric switch receptor, GM18, to improve immunotherapy treatment of solid tumors. The novel receptor is activated by GM-CSF and then works through its IL-18 receptor portion to activate MyD88. That leads to production of a variety of molecules that sustain T cell growth and enhance T cell antitumor response. Tumor-specific chimeric T cells expressing with the novel receptor were more than 10-fold more effective than standard CAR-T cells in preclinical models of pediatric solid tumors.
In murine models for osteosarcoma and Ewing sarcoma, tumors shrank and disappeared in more than 90% of cases at which standard CAR-T cells were ineffective. The new receptor also allowed CAR-T cells to function after repeated re-exposure to tumor cells, which had previously limited the effectiveness of the immunotherapy in treatment of solid tumors.
Work is underway to streamline production of CAR.GM18-T cells. Additional preclinical testing is also planned to assess the safety and effectiveness of GM18 in preclinical pediatric solid tumor models.
Immunotherapy, chimeric antigen receptor (CAR), cancer, solid tumor, brain tumor, T cells, IL18, GM-CSF.
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