# Precise tumor targeting with logic CAR circuits

> **NIH NIH U01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $582,303

## Abstract

Project Summary
 This proposal describes a unique SUPRA CAR system in human T cells to address in vivo off-tumor toxici-
ty, using an established liver transgene expression mouse model. We will use our recently developed split,
universal and programmable (SUPRA) CAR system that simultaneously encompasses multiple critical up-
grades, such as the ability to finely tune T cell activation strength, sense and logically respond to multiple
antigens, and independently regulate two T cell subtypes simultaneously. Specifically, we will evaluate two
types of circuits: (1) AND and (2) NIMPLY (A AND NOT B) logic CAR circuits, which have been determined
bioinformatically as the best type for circuits for discriminating tumors from healthy cells. The proposed exper-
iments will test the hypotheses that (1) our modular and tunable logic CAR T systems are uniquely
suited for preventing on-target off-tumor toxicity in vivo, even when healthy tissues expressing a tar-
get antigen are near the tumor, and (2) the tumor specificity and activity of our SUPRA CAR systems is
enhanced by controlled delivery. Importantly, preliminary data support these hypotheses, and well-
characterized materials and rigorous experimental designs are established in this proposal with essential
cross-disciplinary collaborations and expertise that encompass synthetic biology, immunology, animal tumor
biology, and biomaterials. The specific aims of this five-year proposal are as follows: Aim 1 evaluates AND log-
ic SUPRA CAR specificity in vivo. Aim 2 investigate the tumor specificity and toxicity of NIMPLY logic SUPRA
CAR in vivo. Aim 3 determine the effect of adaptor protein delivery mechanism on tumor-targeting specificity.
Outcomes from this work will establish the clinical potential of logic CAR systems and expand their use to addi-
tional cancers, including solid tumors.

## Key facts

- **NIH application ID:** 10330301
- **Project number:** 1U01CA265713-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Yolonda L Colson
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $582,303
- **Award type:** 1
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330301

## Citation

> US National Institutes of Health, RePORTER application 10330301, Precise tumor targeting with logic CAR circuits (1U01CA265713-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330301. Licensed CC0.

---

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