Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies
7 affiliations
- 1Department of Bioengineering, Rice University, Houston, TX, USA.
- 2Duracyte Inc., Houston, TX, USA.
- 3Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
- 4Division of Microbiology, Tulane National Biomedical Research Center, Covington, LA, USA.
- 5Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA, USA.
- 6Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
- 7Rice Biotechnology Launch Pad, Houston, TX, USA.
Abstract
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.
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BibTeX
@article{fell2026once,
title = {{Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies}},
author = {Cody Fell and Anthony E. Davis and Shalini Pandey and Michael T. Guinn and Zeshi Wang and Jonathon DeBonis and Chancellor Smith and Nathan Brown and Danna Murungi and Yeonju Kim and Imaan Mohandessi and Patrick Bednarz and Amir Ardeshir and Erin M. Haupt and Samuel I. Cuevas and Christy L. Lavine and Michael S. Seaman and Oleg Igoshin and Ravi K. Ghanta and Michael R. Diehl and Omid Veiseh},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aej5440},
url = {https://www.science.org/doi/10.1126/sciadv.aej5440},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies
AU - Cody Fell
AU - Anthony E. Davis
AU - Shalini Pandey
AU - Michael T. Guinn
AU - Zeshi Wang
AU - Jonathon DeBonis
AU - Chancellor Smith
AU - Nathan Brown
AU - Danna Murungi
AU - Yeonju Kim
AU - Imaan Mohandessi
AU - Patrick Bednarz
AU - Amir Ardeshir
AU - Erin M. Haupt
AU - Samuel I. Cuevas
AU - Christy L. Lavine
AU - Michael S. Seaman
AU - Oleg Igoshin
AU - Ravi K. Ghanta
AU - Michael R. Diehl
AU - Omid Veiseh
PY - 2026
DA - 2026/10/02
JO - Science Advances
DO - 10.1126/sciadv.aej5440
UR - https://www.science.org/doi/10.1126/sciadv.aej5440
AB - 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.
SN - 2375-2548
ER -