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Anti-EGFRvIII-SGRP CAR T cells are an experimental "armored" chimeric antigen receptor (CAR) T-cell therapy designed for the treatment of glioblastoma (GBM). These cells are engineered to target the tumor-specific mutation EGFRvIII and constitutively secrete a SIRPγ-related protein (SGRP), which acts as a high-affinity blocker of CD47 (a "don't-eat-me" signal overexpressed by GBM cells). By disrupting the CD47-SIRPα axis, the therapy aims to convert the immunosuppressive tumor microenvironment by activating glioma-associated microglia and macrophages (GAMs) to phagocytose tumor cells. Preclinical studies have demonstrated that locoregional application of these cells can eradicate heterogeneous EGFRvIII-positive and EGFRvIII-negative mosaic tumors, inducing long-term tumor-free survival and overcoming common mechanisms of CAR T evasion such as antigen escape and immune suppression.
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