Abstract / Summary
More than 200 monoclonal antibodies (mAbs) are approved for clinical use, yet their therapeutic potential is constrained by dependence on repeated injections or infusions that drive nonadherence, limit access in low-resource settings, and generate peak-trough pharmacokinetics linked to adverse effects and reduced efficacy. Here, we developed an immunomodulatory, encapsulated cell–based “biologics factory” that overcomes mAb instability, immunogenicity, and the fibrotic foreign body response that have limited previous approaches, enabling continuous in situ production of therapeutic antibodies from a single administration. Screening chemically modified alginate biomaterials in immunocompetent mice identified a lead immunomodulatory alginate formulation that sustains stable serum titers of the HIV-neutralizing mAb 3BNC117 for 1 year. Single-cell RNA sequencing revealed that this formulation promotes a local anti-inflammatory, proresolving immune niche that attenuates fibrosis. The platform’s versatility was demonstrated by the production of 13 diverse mAbs from an allogeneic cell chassis, with sustained in vivo delivery of a subset including ipilimumab, pembrolizumab, adalimumab, and PGT121. Integration into a retrievable macrodevice enabled on-demand therapeutic termination and reimplantation for dose-proportional tuning. In a nonhuman primate, subcutaneous implantation maintained stable ipilimumab titers for more than 6 months with no detectable toxicity, antidrug antibodies, or adverse events, and dose-dependent exposure was confirmed across a three-dose escalation. These results demonstrate a clinically translatable platform that offers a practical strategy to replace frequent injections with single-administration therapy. A cell-based delivery platform within an antifibrotic minimally invasive device enables year-long mAb delivery.