interferon alpha-programmed cell death protein 1 fusion protein

interferon alpha-programmed cell death protein 1 fusion protein is an experimental, tumor-activated immunotherapeutic agent designed to combine the potent anti-tumor activity of Type I interferons with the checkpoint blockade of PD-1 inhibition while minimizing systemic toxicity. The molecule employs a dual-masking architecture where interferon-alpha (IFNα) is integrated into the framework of an anti-programmed cell death protein 1 (PD-1) antibody, sterically hindering both the cytokine and the antibody functions in systemic circulation. Activation occurs specifically within the tumor microenvironment through the proteolytic cleavage of a tumor-selective linker—a mechanism termed spatial reclasp—which restores molecular flexibility and allows for simultaneous IFNα signaling and PD-1 blockade. This localized activation leads to the upregulation of MHC I expression and enhanced T-cell infiltration, potentially overcoming resistance to standard immune checkpoint inhibitors caused by the loss of antigen presentation.

Other names

tumor-activated IFNα-PD-1IFNα-PD-1 fusion proteintumor-activated checkpoint locker