Encapsulated cell therapy for local anti-CTLA-4 delivery in cancer immunotherapy.

Immune checkpoint inhibitors such as anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies have transformed cancer therapy, but their clinical use is often limited by severe systemic toxicities, particularly with anti-CTLA-4. To address this, we developed Myo-P3, a retrievable hollow-fiber encapsulated cell therapy device containing genetically engineered human myoblasts that secrete low doses of anti-CTLA-4 directly into the tumor microenvironment. In a murine colorectal cancer model, peritumoral implantation of Myo-P3 significantly delayed tumor progression and improved survival versus untreated controls. Treatment induced local immune modulation, with early reductions in intratumoral FoxP3+ regulatory T cells and hCTLA-4+ CD4+ T cells, consistent with CTLA-4 blockade, while maintaining substantially lower systemic antibody levels than systemic ipilimumab. Although this model does not permit comprehensive assessment of long-term secretion or toxicity, these data support the feasibility and biological activity of localized anti-CTLA-4 delivery and highlight a controllable, retrievable platform to reduce systemic exposure.