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Engineering B cells to treat and study human disease

Nature Biotechnology volume 43, pages 1431–1444 (2025)Cite this article

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Abstract

Modern cell therapies are designed to harness natural biology to treat a range of complex diseases. The field of immunology has shown that B cells exhibit multiple unique features, including a natural propensity to interact with and regulate other immune cells, a high capacity to produce proteins, and a long cellular lifespan, which are being creatively applied in engineered B cell (eB cell) therapies. In recent years, advances in genome editing technologies and animal modeling have facilitated rapid progress in our ability to study eB cells and execute proof-of-concept studies, thus enabling the first clinical trials of eB cell therapies. In this review, we provide an overview of recent developments in eB cell therapies, including early clinical studies. We discuss challenges to clinical implementation, and promising directions for leveraging B cell biology in future applications for cancer and chronic disease.

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Fig. 1: Leveraging B cell biology to develop eB cells.
Fig. 2: Ex vivo culture to produce eB cells, eBregs and ePCs.
Fig. 3: Strategies to engineer mAbs.
Fig. 4: Animal models to study eB cells, eBregs and ePCs.
Fig. 5: Human ePC engraftment in the BM niche of humanized mice.

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Author notes

  1. These authors contributed equally: Nikita Trivedi, Ragan A. Pitner.

Authors and Affiliations

  1. Seattle Children’s Research Institute, Center for Immunity and Immunotherapy, Seattle, WA, USA

    Nikita Trivedi, Ragan A. Pitner, David J. Rawlings & Richard G. James

  2. Departments of Pediatrics and Immunology, University of Washington, Seattle, WA, USA

    David J. Rawlings

  3. Departments of Pediatrics and Pharmacology, University of Washington, Seattle, WA, USA

    Richard G. James

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  2. Ragan A. Pitner
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Correspondence to Richard G. James.

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Competing interests

R.G.J. and D.J.R. have an equity ownership position in and serve on the scientific advisory board of Be Biopharma. R.A.P., R.G.J. and D.J.R. are credited as inventors of patents filed by Seattle Children’s Research Institute with the United States Patent and Trademark Office regarding technologies described in this article (US20240287452A1, WO2025064484A1, US20230272431A1 and WO2023225447A1).

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Trivedi, N., Pitner, R.A., Rawlings, D.J. et al. Engineering B cells to treat and study human disease. Nat Biotechnol 43, 1431–1444 (2025). https://doi.org/10.1038/s41587-025-02757-y

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