Biology subjects

Murungi, D.

Publications and source records attributed to Murungi, D..

2 recordsLinked to original sources

bioRxiv2026

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.

bioengineering↗

bioRxiv2025

Localized immunomodulation with cytokine-producing cells to mitigate host immune rejection responses in rodents and a non-human primate

The efficacy of cell-based therapeutics is often compromised by host immune recognition of implanted cells and biomaterials, resulting in fibrotic encapsulation and loss of function. Here, we address this challenge with an immunomodulatory cell-based therapy, in which alginate-encapsulated retinal pigment epithelial cells continuously secrete cytokines to locally modulate the implant microenvironment. In a healthy rodent model, the localized production of interleukin-10 (IL-10) or IL-12 from encapsulated cytokine-producing cells prevented host immune rejection and fibrosis of alginate capsules. Mechanistically, treatment was associated with reduced expression of pro-fibrotic genes and immune shifts consistent with macrophage and T-cell regulation, supporting a cytokine-mediated mitigation of foreign body response. In a diabetic murine model (streptozotocin-induced C57BL/6J), co-implantation of human islets with IL-10-producing cells attenuated pericapsular fibrosis, preserved islet viability, and restored normoglycemia for up to 100 days (4.76 times longer than islets alone). Significantly, IL-10-producing cells were also effective in enabling the durability and function of encapsulated cells in a healthy non-human primate, showing translational feasibility. Collectively, these findings suggest that localized cytokine delivery can reduce fibrotic encapsulation and support durable graft function, offering a path to lessen reliance on systemic immunosuppression in islets transplantation and other implantable biomaterial therapies. TeaserEncapsulated IL-10-producing cells locally suppress fibrosis and extend graft function in rodent models and a non-human primate.

bioengineering↗