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PD1-CD28 fusion protein

Development stage
Preclinical
Lead developer
Charité Universitätsmedizin Berlin
Modality
Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes
Administration
Intravenous (via Adoptive T Cell Transfer)
01

Overview

The **PD1-CD28 fusion protein** is a synthetic recombinant immune-modulating protein that combines the extracellular and transmembrane domains of the programmed death receptor-1 (PD-1) with the intracellular signaling domain of the costimulatory receptor CD28. This fusion protein is designed to reprogram the immune checkpoint signaling in T cells, converting the inhibitory signal delivered upon PD-1 ligation by its ligand PD-L1 into a stimulatory, CD28-mediated co-stimulatory signal. CD4+ or CD8+ T cells are genetically engineered (typically via retroviral transduction) to express this fusion receptor, enabling them to resist PD-1/PD-L1-mediated immunosuppression in the tumor microenvironment and promote robust cytokine release, proliferation, and anti-tumor cytotoxicity. This approach has primarily been developed for enhancing adoptive T cell therapies, including CAR-T and TCR-modified therapies, showing efficacy in preclinical models of pancreatic cancer, non-Hodgkin lymphoma, and other PD-L1-expressing tumors[1][2][4][5][6][7][9][10].

Other names
PD-1-CD28 chimeric switch receptorPD1-CD28 chimeric switch receptorPD 1-CD28 chimeric switch receptorimmunomodulatory fusion protein (IFP)PD1-CD28 IFPPD-1-CD28 IFPPD 1-CD28 IFP
02

Targets

CD28 (Cluster of Differentiation 28)PDCD1 (Programmed cell death protein 1 receptor)CD274 (Programmed cell death protein 1 ligand 1)

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