200 Preclinical evaluation of a tandem PD-L1/EphA2 CAR-T cell therapy in multiple solid tumor models
Year: 2026
Type: conference-abstract
Abstract: Background Antigen heterogeneity and the immunosuppressive tumor microenvironment remain major barriers to successful CAR-T cell therapy for solid tumors. We developed tandem PD-L1/EphA2 CAR-T cells to simultaneously target tumor-associated antigens and immune evasion. Simultaneous targeting of PD-L1 and EphA2 may reduce antigen escape while addressing immune suppression within the tumor microenvironment. This study evaluated their preclinical antitumor activity, dose-response relationship, persistence, and safety in multiple solid tumor models.Methods Tandem PD-L1/EphA2 CAR-T cells were manufactured using a GMP-relevant manufacturing process with a clinical-scale lentiviral vector and the G-Rex 100M Closed system. NOG mice bearing Hep3B hepatocellular carcinoma, SNU601 gastric cancer, or OVCAR5 ovarian cancer xenografts received a single intravenous infusion of vehicle, mock T cells, or tandem CAR-T cells at Low (2.0×10 5), Mid (1.0×106), or High (3.0×106) doses (n = 9–10/group). Tumor growth, complete response (CR; defined as a tumor volume of 1 mm3), CAR-T persistence, and safety were evaluated. Independent GLP toxicity studies were performed by the Korea Testing & Research Institute (KTR).Results Tandem PD-L1/EphA2 CAR-T cells produced dose-dependent tumor regression across all models. In the Hep3B model, complete tumor regression was observed in all male mice at all dose levels, while CR rates were 50% at the Low dose and 100% at the Mid and High doses in female mice. In the SNU601 model, tumor growth was inhibited, with CR rates reaching 30% in males and 20% in females in the Mid-dose group. In the OVCAR5 model, the High-dose group achieved an 80% CR rate. CAR-T cells were detected in peripheral blood and tumor tissues throughout the 4-week observation period in a dose-dependent manner. No treatment-related toxicity was observed at the Low or Mid doses. Dose-limiting toxicity, including late-onset body weight loss and mortality, was observed only in the High-dose group.Conclusions Tandem PD-L1/EphA2 CAR-T cells produced consistent antitumor activity across hepatocellular, gastric, and ovarian cancer models, with durable CAR-T persistence and an acceptable therapeutic window. These findings support further evaluation of this tandem CAR-T strategy for the treatment of solid tumors.
Institution: Chonnam National University Hwasun Hospital
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225199782