Once yearly cell-based therapy for sustained and dose tunable delivery of monoclonal antibodies
Over 200 monoclonal antibodies (mAbs) are approved for clinical use, yet their therapeutic potential is constrained by dependence on repeated injections or infusions that drive non-adherence, 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 one year. Single-cell RNA sequencing revealed that this formulation promotes a local anti-inflammatory, pro-resolving immune niche that attenuates fibrosis. The platforms versatility was demonstrated by production of thirteen 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 re-implantation for dose-proportional tuning. In a non-human primates, subcutaneous implantation maintained stable ipilimumab titers for over six months with no detectable toxicity, anti-drug antibodies, or adverse events, and dose-dependent exposure was confirmed across a three-dose escalation. These results demonstrate a clinically translatable platform offering a practical strategy to replace frequent injections with single-administration therapy.