Reltecimod T-cell-specific surface glycoprotein CD28 (TP44) antagonist CD28 homodimer interface mimetic peptide Treatment of necrotizing soft-tissue infection

摘要

Necrotizing soft-tissue infections (NSTIs) are uncommon but devastating infections associated with significant morbidity, mortality and medical resource utilization. Unlike less severe skin infections, NSTIs involve both local and systemic disease manifestations. The systemic response is the culmination of a host response to infection that, while initially appropriate, becomes dysregulated. The augmented release of proinflammatory cytokines correlates with NSTI severity and can lead to shock, multiorgan failure and death. Currently, no therapies are specifically approved to treat NSTI. Reltecimod is a synthetic peptide antagonist of both superantigen exotoxins and the CD28 T-cell costimulatory receptor that is under development for the treatment of NSTI. In animal models of infection, it has been shown to have a broad spectrum of activity, protecting from the overproduction of cytokines. A phase II study demonstrated the safety of reltecimod in NSTI patients, and, compared to placebo, consistent improvement in clinical status across multiple endpoints. An ongoing phase III study is evaluating the efficacy of reltecimod using a composite end-point of clinical parameters resulting from NSTI. This review will focus on the pathophysiology of NSTI and the development of reltecimod as a novel treatment.