# Hijacking the T cell machinery for logic-gated CAR T cell control

> **NIH NIH DP2** · STANFORD UNIVERSITY · 2021 · $800,041

## Abstract

Project Summary
Solid tumors are the most common cause of cancer death in the United States. Chimeric antigen receptor (CAR)
T cells have revolutionized the care of relapsed and refractory B cell malignancies but have not yet mediated
substantial benefit for patients with solid tumors. CARs redirect the powerful anti-tumor activity of a T cell against
a tumor cell by targeting an antigen expressed on its surface. In solid cancers, most target antigens are shared
with normal, vital tissues, and therefore CARs can mediate dangerous and potentially fatal toxicity. This has
prevented widespread application of CAR T cells to solid tumors. The current generation of CAR T cells is unable
to differentiate between tumor tissue and normal tissue largely because they rely on a single input/single output
system that activates whenever the T cell finds its target. We have generated a novel mechanism to direct the
CAR T cell response only when multiple antigens are present, greatly enhancing our ability to generate a
programmed immunotherapeutic response against solid tumors. Optimization and application of this platform will
greatly enhance the number of potential targets for CAR T cells, a paradigm shifting technology poised to mediate
significant clinical benefit for patients with solid tumors. This strategy will also prove essential to effectively use
CAR T cells to treat other cancers, such as myeloid malignancies, and diseases as diverse as autoimmunity and
fibrosis. The novel system proposed here has the potential to redefine the landscape for programmable cellular
therapies.

## Key facts

- **NIH application ID:** 10246119
- **Project number:** 1DP2CA272092-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Robbie G. Majzner
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $800,041
- **Award type:** 1
- **Project period:** 2021-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246119

## Citation

> US National Institutes of Health, RePORTER application 10246119, Hijacking the T cell machinery for logic-gated CAR T cell control (1DP2CA272092-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246119. Licensed CC0.

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