# Transposon Engineered B Cell Therapy for Hunter Syndrome

> **NIH NIH R43** · IMMUSOFT CORPORATION · 2020 · $466,804

## Abstract

PROJECT SUMMARY
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked recessive lysosomal disease caused
by the absence of iduronate-2-sulfatase (IDS), resulting in systemic accumulation of glycosaminoglycan (GAG)
storage materials, hepatosplenomegaly, skeletal dysplasias, cardiopulmonary obstruction, progressive
neurologic impairment and death by age 12. MPS II is currently treated by enzyme replacement therapy, but
these treatments are extraordinarily expensive and do not fully address the physiologic and neurologic
manifestations of the disease. Here we propose an entirely novel approach to the treatment of MPS II.
Immusoft Corp. is developing genetically engineered autologous human B cells for production of therapeutic
proteins upon infusion into patients. Immusoft is using the Sleeping Beauty (SB) transposon system for
integrative gene transfer and expression, as developed by Discovery Genomics, Inc. (DGI). In 2016 Immusoft
acquired DGI, and here we propose to combine Immusoft’s novel B cell expression platform with the SB
transposon technology for the purpose of expressing human IDS from B cells in vivo as an approach to achieve
systemic and CNS-directed expression of IDS as a treatment for MPS II. This project is further strengthened by
the extensive experience of Immusoft’s investigative team and colleagues at the University of Minnesota in the
conduct of preclinical studies and clinical trials of new treatments for lysosomal diseases, including MPS II. For
this Phase I study, the Specific Aims are; (i) Correction of IDS deficiency in a murine model of MPS II by
adoptive transfer of human B cells genetically engineered to express human IDS using the Sleeping
Beauty transposon system. IDS expressing human B cells will be infused into immunodeficient NSG MPS II
mice recently established in the laboratory of the PI, evaluating recipient animals for adoptive transfer,
expression and distribution of IDS activity, and correction of neurologic and physiologic disease. Treated animals
will be evaluated for prevention of neurocognitive deficiency, skeletal defects and metabolic disease as a model
for potential effectiveness in the treatment of human MPS II. (ii) Modification of B cells to promote
transmigration of the blood-cerebrospinal fluid (CSF)-barrier. Human B cells will be genetically modified
with SB transposons encoding CCR6 or CCR7, chemokine receptors that are known to mediate T-cell migration
from the blood into the CSF. These transposed B cells will be tested for the ability to cross the blood-CSF-barrier
using an in vitro transmigration assay, mimicking conditions at the blood-CSF barrier, and evidence for
engineered B cell penetration of the CNS as a cellular vehicle for delivery of therapeutics for neurologic disease,
including MPS II. Results from these studies will be directly applicable to the development of a clinical
protocol for treatment of human MPS II by infusion of B cells genetically engineered to expres...

## Key facts

- **NIH application ID:** 10087218
- **Project number:** 1R43NS120264-01A1
- **Recipient organization:** IMMUSOFT CORPORATION
- **Principal Investigator:** CHRISTIANE S HAMPE
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,804
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087218

## Citation

> US National Institutes of Health, RePORTER application 10087218, Transposon Engineered B Cell Therapy for Hunter Syndrome (1R43NS120264-01A1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10087218. Licensed CC0.

---

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