Engineered B Cells to Control Hyperactive Immunity

Technology Overview

Dr. Richard G. James

Adverse immune responses cause autoimmune conditions; lead to rejection of organ transplants; and reduce the effectiveness of gene, cell and protein therapy. Currently, these clinical challenges are managed by broad suppression of B- and T-cell responses or by global depletion of a patient’s B cells. Engineered B cells can suppress immune responses to specific antigens, thereby providing a targeted approach to immune suppression that spares healthy B and T cells.

Bioengineer Richard James, PhD, is an expert in immunotherapy and genome editing. His lab developed advanced techniques for engineering B cells and is using these methods to generate B cells that selectively modulate the immune system. This innovative approach to immune modulation can increase or reduce immune responses in a more targeted, less damaging way than is possible with currently available therapies.

Antigen-specific decoy B cells to induce immune tolerance and selectively silence therapy-neutralizing antibodies

As a first application of this novel, targeted immune-modulation strategy, the James Lab is generating “decoy” B cells. The decoys are designed to selectively silence an unwanted immune response by blocking development of therapy-neutralizing antibodies. By preserving normal immunity to other antigens, this approach avoids the adverse effects of broader immune suppression therapies that eliminate a patient’s protective immunity, which increases their risk of infection and cancer.

The decoy B cells are engineered to express a B-cell receptor with high affinity for an antigen that should be tolerated by the patient. The decoys are modified so they cannot secrete antibody against the antigen. All other B-cell functions are normal, so the decoys localize to lymphoid centers where B cells mature into antibody-producing cells. At lymphoid centers, decoy B cells compete for space and resources with endogenous B cells that also bind the same antigen. This competition prevents endogenous B cells from maturing into antibody-secreting cells, thereby suppressing antibody production against the target.

Proof-of-concept studies in an animal model show that decoy B cells primed with a specific antigen localized to lymphoid tissues. There, they outcompeted endogenous B cells with lower affinity for the antigen by occupying more physical space in lymphoid centers; compared with the endogenous B cells, the decoy B cells expanded into a larger population. The James Lab further demonstrated the therapeutic potential of decoy B cells by showing suppression of therapy-neutralizing antibodies against factor VIII. Crucially, protective immunity to other antigens was preserved.

Dr. James has extensive experience with industry collaborations and leadership at start-up companies. In addition to engineering B cells for a variety of clinically relevant applications including systemic and local drug delivery, he has expertise in modeling protein variants and tumors. He is interested in industry partnerships to advance B-cell engineering and B cells for therapeutic uses, including through clinical trials.

Who should partner with us?

• Programs limited by antidrug antibodies or neutralizing antibody responses.
• Transplant or autoimmune programs seeking antigen-specific tolerance without immunosuppression.
• Programs in gene, cell or protein therapies involving therapy-directed immunity.

Learn More

• Richard James, PhD, Seattle Children’s Research Institute
• James Lab
• The immune control platform complements our engineered B-cell delivery, humanized small animal modeling and variant discovery platforms for end-to-end discovery for translation partnerships.

Stage of Development

• Preclinical in vitro: control of antigen-specific T-cell responses by engineered B cells
• Preclinical in vivo: proof-of-concept for tolerance induction and immune amplification in syngeneic disease models

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Consultation agreement
• Licensing agreement
• Collaborative animal model development

Publications

1. Trivedi N, Pitner RA, Rawlings DJ, James RG. Engineering B cells to treat and study human disease. Nat Biotechnol. 2025;43(9):1431-1444.
2. Pitner RA, Chao JL, Dahl NP … James RG, et al. Blunting specific T-dependent antibody responses with engineered “decoy” B cells. Mol Ther. 2024;32(10):3453-3469.
3. Hill TF, Narvekar P, Asher GD … James RG. Human plasma cells engineered to secrete bispecifics drive effective in vivo leukemia killing. Mol Ther. 2024;32(8):2676-2691.
4. Hung KL, Meitlis I, Hale M … James RG. Engineering protein-secreting plasma cells by homology-directed repair in primary human B cells. Mol Ther. 2018;26(2):456-467.

Last updated August 2026