# Developing Monoclonal Antibody Secreting Human Plasma Cells to Provide Long-Lasting EBV Immunity in Humanized Mice

> **NIH NIH F30** · UNIVERSITY OF WASHINGTON · 2024 · $53,974

## Abstract

ABSTRACT
Monoclonal antibody (mAbs) therapies have proven to be effective treatments for a multitude of clinical
applications. Several of these treatments require repeated administration through intravenous infusions leading
to high costs and poor patient adherence. A new field has emerged that seeks to generate mAb-secreting
plasma cell therapeutics that could be administered once to provide lifelong therapeutic mAb levels as a
therapeutic alternative. Plasma cells have high secretory capacities, can last a lifetime and are thought to be
relatively quiescent. Advances in gene editing and ex vivo B cell differentiation have enabled the ability to
generate plasma cells that secrete an exogenous mAb. However, current gene editing strategies do not fully
account for endogenous antibody expression or control for what isotype the exogenous mAb is expressed as.
Additionally, the field of gene-edited human plasma cell lacks both large and small animal models to test the
engraftment and functionality of these mAb-secreting plasma cells.
Aim 1 of this proposal will use a new gene engineering strategy to generate a human plasma cell therapeutic
that secretes an engineered IgG mAb against Epstein Barr Virus (EBV) as a proof of concept for future mAb-
secreting cell therapies. I will characterize the ability of gene-edited primary plasma cells to produce large
quantities of defined mAbs and compare to previously published methods. Human plasma cells are difficult to
engraft in small animal models due to the lack of extrinsic survival factors from human stromal and myeloid
cells. Aim 2 of this proposal will use a humanized (NSG-huCD34) mouse model to better predict the potential
engraftment potential of gene-edited plasma cells therapies. This humanized mouse model also serves as a
model for human-tropic EBV infection. I propose to validate the functionality of anti-EBV secreting plasma cells
by showing that these cells protect humanized mice against high dose intravenous EBV challenge. This would
be the first time that gene-edited primary human plasma cells were shown to protect against a human-tropic
disease in a humanized mouse model and would serve as a proof of concept for use of gene-edited plasma
cells to provide mAbs.
This project is ideal for my training as a young physician scientist due to my strong interest in translational
immunology, the complementation of my previous training in chimeric antigen receptor- modified T cell
research, the extensive background of Dr. David Rawlings and Dr. Richard James in B cell biology and
mentorship, and the quality research and medical education at the University of Washington. The activities
detailed in this proposal will provide a strong background for a future career as a physician scientist pursuing
translational immunology research.

## Key facts

- **NIH application ID:** 10687192
- **Project number:** 5F30AI164574-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Tyler F Hill
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2021-09-16 → 2025-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687192

## Citation

> US National Institutes of Health, RePORTER application 10687192, Developing Monoclonal Antibody Secreting Human Plasma Cells to Provide Long-Lasting EBV Immunity in Humanized Mice (5F30AI164574-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10687192. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*