Cytokine release syndrome (CRS) is a well-recognized complication of T cell-based cancer immunotherapies, affecting the majority of patients to some degree. Severe CRS occurs in approximately 2–23% of patients. Current management relies on broad immunosuppression, which can blunt anti-tumor efficacy and lacks specificity for the pathogenic cell populations driving toxicity. To address this unmet need, we developed a novel platform that redirects innate immune effectors to selectively deplete antigen-specific T cells responsible for CRS. Our Innate Immune Cell Redirectors (IICRs) are engineered Fc-fusion proteins comprising (1) a covalent peptide-MHC module that engages cognate T cell receptors on target T cells and (2) an innate immune cell engaging domain. This architecture enables antigen-specific depletion of pathogenic T cells while preserving the broader immune repertoire. As proof of concept, pre-existing or expanded CMV+ CD8+ T cells in human PBMCs were efficiently depleted by IICRs bearing the CMV pp65 peptide and an anti-CD16 alpha (FcγRIII alpha) scFv for antigen-specific T cell and innate immune cell engagement, respectively. Multiple IICRs can be combined to simultaneously deplete expanded CMV+ and SARs+ T cells, enabling broader toxicity control. This modular platform is readily adaptable to diverse TCR specificities and may serve as a failsafe for the depletion of TCR-T cells and peptide-centric CAR T cells to manage unanticipated CRS and related toxicities.