# The development of a GMP eDHFR vector to monitor investigational CAR T cell therapies

> **NIH NIH R41** · VELLUM BIOSCIENCES LLC · 2024 · $300,000

## Abstract

Abstract
The development of cell and gene therapies like Chimeric Antigen Receptor (CAR) T cells has necessitated new
technologies that can monitor the biodistribution and trafficking pattern of these therapies in human patients.
Imaging is particularly well suited to provide quantitative measurements of such therapies over time. Vellum
Biosciences is a platform imaging company geared to fill this void in available technologies, providing repeatable,
robust, and sensitive measures of genetic medicine in situ with clear applications in new drug development,
clinical research, and eventually, clinical practice. Vellum’s technology is based on positron emission tomography
(PET) radiotracer derivatives of the synthetic antibiotic trimethoprim (TMP) and engineered expression of its
protein target E. coli dihydrofolate reductase (eDHFR). When eDHFR is expressed via a genetic medicine (e.g.,
cells harboring lentiviral or adeno-associated viral vectors or therapeutic mRNA), TMP radiotracers can be used
to measure the expression of the protein products in any tissue within the body. Our strategy has been used to
monitor the trafficking of CAR T cells targeting several types of tumors in rodents in collaboration with several
different research groups at the University of Pennsylvania (UPenn) and a global pharmaceutical company. In
this STTR phase 1, we propose the development of a GMP-compliant eDHFR viral vector that can be applied in
a modular fashion to different cellular therapies to monitor their biodistribution over time. This “stand-alone”
imaging vector dovetails with Vellum and UPenn’s on-going collaborative STTR Phase I grant focused on
optimizing [18F]-FTMP production to provide a commercial supply of the radiotracer (R41EB034141). In Aim 1,
we will evaluate the feasibility of using a stand-alone imaging vector format in vitro, which can then be applied
to different cellular therapies in collaboration with the Penn Center for Cellular Immunotherapies (CCI). In Aim
2, we take the enabling steps to perform quality control measures and functional assessment of the vector both
in vitro and in vivo and take the necessary steps to manufacture a GMP-compliant eDHFR lentiviral vector. This
process has been initiated via an established relationship with a CRO to produce the IND-ready DNA plasmids
in collaboration with the CCI and with the “line-of-sight” assistance of the Penn Vector Core for the future clinical
grade lentivirus. Taken together, these short-term aims will provide the evidence base needed for the final
justification and creation of eDHFR viral vectors that allow monitoring of investigational cell therapies in patients
at UPenn. We envision that our approach will substantially impact our understanding of why a cell therapy
product is successful or fails on an individual patient level using non-invasive imaging.

## Key facts

- **NIH application ID:** 11007670
- **Project number:** 1R41AI186797-01
- **Recipient organization:** VELLUM BIOSCIENCES LLC
- **Principal Investigator:** Derek Miller
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2024-08-07 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11007670

## Citation

> US National Institutes of Health, RePORTER application 11007670, The development of a GMP eDHFR vector to monitor investigational CAR T cell therapies (1R41AI186797-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11007670. Licensed CC0.

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