Novel Preclinical Models for Evaluating Checkpoint Inhibitor Resistance

Resistance to PD-1/PD-L1 checkpoint inhibitors remains a major obstacle in cancer immunotherapy. GemPharmatech has developed a comprehensive panel of preclinical anti-PD-1 resistance models, including drug-induced, genetically engineered, and primary resistance systems. Drug-induced resistance was established through chronic anti-PD-1 treatment and serial tumor re-implantation in BALB/c-hPD-1 humanized mice. Genetically engineered models included CT26 tumors with B2M or STK11 knockout. These resistant tumors exhibited distinct immunosuppressive microenvironments, characterized by reduced CD8⁺ T-cell infiltration and expansion of suppressive myeloid cells. Collectively, these well-characterized models serve as valuable translational tools to dissect resistance mechanisms, identify biomarkers, and develop next-generation immunotherapy strategies.