# CAR T cells for tumor drug delivery

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $22,048

## Abstract

Project Summary/Abstract
Chimeric antigen receptor (CAR) T cells are engineered ex- vivo to localize to tumors and kill antigen positive
cancer cells. This project has a direct relationship to health because CAR T cell therapy has shown
promise for treating B cell malignancies, but many barriers limit their efficacy in solid tumors, such as antigen
heterogeneity and an immunosuppressive tumor microenvironment. The long-term objectives of this project
is to engineer a CAR T cell that can overcome these obstacles. To overcome these obstacles, we combined
enzyme-prodrug systems with CAR T cells, generating Synthetic Enzyme Armed KillER (SEAKER) CAR T
cells. We engineered human CAR T cells to secrete an enzyme, β-Lactamase, which cleaves cephalothin
chemical motifs. We also synthesized cephalothin-linked prodrugs of cytotoxic agents. SEAKER cells deliver
β-Lactamase to the tumor, to selectively unmask systemically administered, nontoxic cephalothin prodrugs in
the tumor microenvironment. Our lab is the first to demonstrate that cellular therapeutics can generate small
molecule drugs at the tumor site in xenograft studies (paper submitted). However, mice used in xenograft
studies lack a complete immune system. Therefore, how SEAKER cells interact with a complete, endogenous
immune system are not understood. Thus, we will transition our SEAKER platform to fully immunocompetent,
syngeneic mouse models to inform clinical application of our technology. Our lab has already characterized
murine SEAKER cells, in vitro, and has demonstrated the compatibility of the SEAKER platform with murine
cells. The specific aims are:
Aim 1: Characterize SEAKER cell kinetics and biodistribution in syngeneic in vivo models.
Aim 2: Demonstrate improved anti-tumor efficacy of our SEAKER platform over traditional CAR-T cells in a
fully immunocompetent host.
The research environment is exceptionally well suited for my goals.This research will be completed at
Memorial Sloan-Kettering Cancer Center (MSKCC) and Weill Cornell Medicine (WCM), two prominent
institutions with track-records in training successful scientists. MSKCC is a world leader in CAR T cell therapy.
The training plan of myself, the applicant, will maximize my potential to achieve the goals for this fellowship
and prepare me for an academic career. I have experience in many necessary techniques to complete the
proposed research. I have an extensive network of collaborators and peers who can aid the development of
new techniques to complete this proposal. I am a PhD candidate, and have completed my required
coursework. I have a strong commitment to diversity and will continue to promote equality in biomedical
research.

## Key facts

- **NIH application ID:** 10217035
- **Project number:** 5F31CA254331-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Christopher Bourne
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $22,048
- **Award type:** 5
- **Project period:** 2020-07-07 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217035

## Citation

> US National Institutes of Health, RePORTER application 10217035, CAR T cells for tumor drug delivery (5F31CA254331-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10217035. Licensed CC0.

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