Programmed cell death 1-CD28 chimeric switch receptor (PD-1-CD28 CSR) (PD-1-CD28 CSR)

The Programmed cell death 1-CD28 chimeric switch receptor (PD-1-CD28 CSR) is a synthetic fusion protein designed to enhance the efficacy of adoptive cell therapies, such as CAR-T or TCR-T cells, in the immunosuppressive tumor microenvironment (Liu et al., 2016, Cancer Res). It consists of the extracellular domain of the inhibitory receptor PD-1 fused to the transmembrane and cytoplasmic signaling domains of the costimulatory receptor CD28 (Schlenker et al., 2013, Cancer Res). In many cancers, tumors upregulate PD-L1 to trigger the PD-1 pathway in T-cells, leading to exhaustion and immune evasion. By expressing the PD-1-CD28 CSR, T-cells can recognize PD-L1 on tumor cells and, instead of being inhibited, receive a potent costimulatory signal that promotes proliferation, cytokine production, and sustained anti-tumor activity (Yao et al., 2022, J Hematol Oncol). This switch mechanism is particularly relevant for treating solid tumors where the PD-1/PD-L1 axis is a major barrier to successful immunotherapy. Clinical and preclinical studies have demonstrated that this approach can significantly improve the persistence and metabolic fitness of engineered T-cells (Kobold et al., 2015, J Natl Cancer Inst).

Other names

PD1-CD28 switch receptorPD-1/CD28 fusion receptorChimeric PD-1:28 receptorPD-1-CD28 costimulatory receptor

The receptor binds to PD-L1 via its PD-1 extracellular domain and transmits a costimulatory signal through its CD28 intracellular domain, effectively converting an immunosuppressive signal into an activating one for T-cells.