# Quantitative control of CAR T cells via image-guided delivery and monitoring

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $651,868

## Abstract

Abstract- CONFIDENTIAL
To provide a means for quantitative control of CAR T cell activity, our team first created universal immune
receptors (UnivIRs), a versatile platform for the de novo generation and quantitative control of tumor antigen-
specific T cells where human T cells are genetically engineered with novel docking immune receptors and can
be conferred with highly personalized tumor specificity through the subsequent loading/re-targeting with
“tagged” antigen-specific antibodies, scFvs or other receptor ligands. Building upon these principles, we have
created an orthogonal image-guided T cell delivery (IGTD) method where localization of the targeting ligand
and delivery of CAR T cells with tailored payloads are guided and monitored through noninvasive imaging in
order to facilitate safe and effective targeted therapy for cancer. Our theranostic IGTD platform utilizes novel
targeting biologics with covalent binding tags that can be imaged, or engaged by CAR T cells to activate their
antigen-specific anti-tumor response. These targeting biologics can be used for diagnostic imaging prior to
CAR T cell delivery, to assess localization of the agent to the tumor, predict response to therapy, and evaluate
for potential on-target off-tumor toxicity. In addition, our IGTD method will permit in vivo cell tracking via direct
radiolabeling of CAR T cells prior to infusion, or via a small molecule PET imaging probe that binds the CAR
construct on the T cells. Our multidisciplinary team's goal is to optimize this IGTD method to allow local, image-
guided delivery of the therapeutic T cell product to the target tissue, to allow localized and controlled delivery of
immunomodulatory agents for maximal activity and safety, and to provide functional imaging readouts on the
therapeutic process(es) that occur during treatment. We build upon strong preliminary results to test the central
hypothesis that CAR therapy can be improved by targeting multiple and diverse antigens either simultaneously
or sequentially and safely applied through integrated pre-therapeutic diagnostic imaging and innovative CAR
platform re-development. By uniting diverse scientific expertise in advanced T cell gene-engineering with
molecular imaging and chemistry, we propose to 1) develop, test and optimize novel universal immune
receptors that uniquely and covalently bind tagged and image-labeled TAA-specific antibodies to recapitulate
CAR architecture and activity in vivo; 2) evaluate their potential to simultaneously attack multiple TAAs on
tumor cells as well as suppressive cells in the microenvironment to maximize outcome, 3) develop radiolabeled
antibody-based diagnostic PET/CT imaging to measure antibody localization to tumor and TAA biodistribution
prior to universal CAR T cell administration and test for its ability to predict safety and response; and 4) serially
monitor and understand universal CAR T cell distribution in tumor and healthy organs using PET-based “live”
in vivo ...

## Key facts

- **NIH application ID:** 9994896
- **Project number:** 5R01EB026892-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michael David Farwell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $651,868
- **Award type:** 5
- **Project period:** 2018-09-30 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994896

## Citation

> US National Institutes of Health, RePORTER application 9994896, Quantitative control of CAR T cells via image-guided delivery and monitoring (5R01EB026892-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994896. Licensed CC0.

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