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αPD-1-IL-2x is a bifunctional recombinant fusion protein designed for cancer immunotherapy. It consists of a monoclonal antibody targeting the checkpoint receptor Programmed cell death protein 1 (PD-1) fused to a modified Interleukin-2 (IL-2) cytokine, specifically a "No-α" mutein. This modification prevents the IL-2 component from binding to the high-affinity IL-2 receptor alpha subunit (IL-2Rα/CD25), a strategy intended to reduce the activation of immunosuppressive regulatory T cells (Tregs) and mitigate systemic toxicities such as vascular leak syndrome. By targeting PD-1, the fusion protein preferentially delivers IL-2 signaling to tumor-specific PD-1+ effector T cells. In preclinical studies, αPD-1-IL-2x has been used as a benchmark "leading" fusion protein to evaluate the therapeutic window of next-generation immunotherapies. Research indicates that while it provides anti-tumor activity, it can still induce significant systemic side effects, including body weight loss and severe splenomegaly, at relatively low doses (e.g., 1.25 mg/kg) compared to newer engineered variants.
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