This study developed a chimeric PD1 (chPD1) receptor by fusing the extracellular domain of PD1 with the intracellular signaling domains of Dap10 and CD3ζ. T cells expressing this chPD1 receptor were tested across various syngeneic murine models of solid tumors, including melanoma, pancreatic, renal, colon, liver, prostate, bladder, and breast cancers. The chPD1 T cells effectively lysed PD-L1/PD-L2-expressing tumor cells, secreted pro-inflammatory cytokines (e.g., IFN-γ, TNF-α, IL-2, GM-CSF, IL-17, IL-21), and led to long-term tumor-free survival. Additionally, treatment induced protective host anti-tumor memory responses without significant off-target effects on healthy tissues.
ChPD1 T cells demonstrated potent anti-tumor activity across multiple solid tumor models, induced durable immune memory, and exhibited minimal toxicity to normal tissues, highlighting their potential as a universal CAR T-cell therapy for solid tumors.
Syngeneic immunocompetent mouse models (e.g., C57BL/6, BALB/c) bearing PD-L1/PD-L2-expressing tumors; T cells were genetically modified to express the chPD1 receptor.
Cancer immunotherapy, Chimeric antigen receptor (CAR) T cells, PD1 ligands, Solid tumors, T cell activation
Syngeneic mouse models, Chimeric receptor engineering, T cell transduction, Immunocompetent tumor models
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
