Transcriptomic profiling of tumors in treatment-naive, homologous recombination-proficient (HRP) ovarian cancer PDX model

CAR-T cell therapy remains ineffective in most solid tumors, partially due to insufficient infiltration. Bridging therapy administered between apheresis and CAR-T cell infusion could control tumor progression and remodel the tumor microenvironment without impairing CAR-T cells. Here, we evaluated the potential of PARP inhibitors plus anlotinib as bridging therapy in ovarian cancer. In ovarian tumors-bearing immunocompetent mice, this combination induced sustained T cell infiltration, associated with activated cGAS-STING pathway, vascular normalization, and reduced collagen deposition. We engineered TGFb-resistant MSLN/CD19 dual-target CAR-T cells based on bait-and-switch design. Bridging therapy significantly enhanced CAR-T cell infiltration and antitumor activity across multiple preclinical ovarian cancer models. These findings informed a phase I clinical trial (NCT05141253) assessing this bridging therapy in patients with ovarian cancer. Collectively, this study established a clinically actionable bridging therapy with immediate translational potential in ovarian cancer and highlighted bridging therapy as an opportunity to potentiate CAR-T cells in solid tumors.