Immunotherapy and Biologic Development Using Preclinical Models

Technology Overview

Many of today’s most promising new therapies fail because existing animal models do not faithfully recapitulate the human immune system. Current models often cannot replicate tissue targeting by therapeutics or the effects of long-term drug exposure.

Why use humanized small animal models for translational immunotherapy?

• Human-relevant immune biology enables evaluation of therapies in the context of human immune cells.
• Mechanism of action insights determine how cell and biologic therapies function in vivo.
• Pharmacokinetic/pharmacodynamic (PK/PD) modeling supports dose, durability and exposure response studies.
• De-risking translation results from identifying failures before costly clinical trials.

Dr. Richard G. James

Bioengineer Richard James, PhD, is an expert in generating humanized small animal models. His lab builds specialized platforms of humanized models and resources such as reporter cells and assays for mechanistic and translational evaluation of human immune-based therapies in vivo. The animal models can be custom engineered to advance the development of any new drug, including biologics such as chimeric antigen receptor (CAR) T cells, other engineered immune cells and monoclonal antibodies. Applications of the animal model work include developing and improving protein-replacement and gene therapies.

Platform capabilities include:

• NSG-huCD34 immunodeficient animals that are engrafted with human CD34+ hemopoietic stem cells and with patient-derived xenografts or allogeneic engineered immune cells.
• Small animal models with human cytokine-supported niches that sustain antibody-secreting cells in vivo.
• Models of B cell malignancy, gut inflammation and central nervous system (CNS) disorders.

Using these animal models, the James Lab demonstrated:

• Durable engraftment and function of engineered human plasma cells.
• In vivo persistence and secretion of therapeutic antibodies and enzymes by engineered B cells.
• Antitumor activity of engineered B cell products against patient-derived leukemia xenografts.
• Pharmacologic control of human B cell-driven lymphoproliferative disease.
• Elimination of pathogenic human plasma cells and circulating antibodies using regulated B cell-maturation antigen (BCMA)-targeting CAR T cells.

Therapeutic modalities supported by these platforms include:

• Tumor-targeting CAR T-cell or natural killer (NK)-cell products.
• Antibody-secreting plasma cells for long-term systemic or localized delivery of biologics.
• Drugs that interrupt tumor-immune interactions.
• Proteins for enzyme replacement.
• Gene therapy agents.
• Immune modulation therapy for autoimmune and inflammatory conditions, transplant rejection, graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorders (PTLD).
• Biologics that work across the blood-brain barrier.

Dr. James has extensive experience with industry collaborations and leadership of start-up companies. His expertise includes engineering B cells for systemic and localized drug delivery and for immune modulation, as well as modeling of protein variants. He is interested in using his humanized small animal model expertise to work with industry partners on disease-specific animal model development; evaluating cell, gene and biologic therapies; determining mechanisms of action; and performing PK/PD studies.

Who should partner with us?

• Cell therapy developers seeking human-relevant in vivo efficacy and persistence data.
• Industry researchers on biologic and gene therapy projects who need PK/PD and tissue-targeting validation.
• Leaders of programs stalled by poor translational performance of existing animal models.

Stage of Development

• Preclinical in vitro: complementary reporter cell and functional assay development.
• Preclinical in vivo: multiple humanized and syngeneic small animal platforms.

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Consultation agreement
• Contracted collaboration
• Collaborative animal model development

Learn More

• Richard James, PhD, Seattle Children’s Research Institute
• James Lab
• The humanized small animal model platforms complement these James Lab programs for end-to-end, discovery-to-translation partnerships: engineered B cell delivery (systemic and local), immune control and variant discovery.

Publications

1. Hill TF, Helmers AE, Cheng RY … James RG. Humanized mice enable in vivo evaluation of engineered plasma cell biology and therapeutic function. Mol Ther Methods Clin Dev. 2026; 34(1):201666.
2. Zhang TT, Cheng RY, Ott AR … James RG. BCR signaling is required for posttransplant lymphoproliferative disease in immunodeficient mice receiving human B cells. Sci Transl Med. 2024;16(742):eadh8846.
3. 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.
4. Honaker Y, Gruber D, Jacobs C … James RG, et al. Targeting human plasma cells using regulated BCMA CAR T cells eliminates circulating antibodies in humanized mice. Mol Ther. 2025;33(6):2819-2833.
5. Cheng RY, Hung KL, Zhang T … Rawlings DJ, James RG. Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment in vivo. Nat Commun. 2022;13(1):6110.  

Last updated August 2026