# OR2H1 is an effective target for CAR T cells in human epithelial tumors

> **NIH NIH R21** · DUKE UNIVERSITY · 2024 · $213,852

## Abstract

ABSTRACT
 Identifying accessible tumor antigens that are not expressed in vital organs would allow genetic
engineering of CAR T cells to avoid dysfunction at tumor beds. We have identified an olfactory receptor (OR)
expressed in a variety of human tumors, ranging from ~70% of intrahepatic cholangiocarcinomas and 39% of
prostate cancers, to ~10% of NSCLCs, and generated CAR T cells that specifically target its extracellular domain.
The long-term goal of these studies is to translate these CAR T cells. Here, we will advance the preclinical work
needed to apply for IND approval for a first-in-human clinical trial conducted at Moffitt, using OR2H1 CAR T cells
generated in our Cell Therapy Facility under GMP conditions. Our central hypothesis is that genetically
engineered OR2H1 CAR T cells can effectively control the progression of established tumors of different
histologies, without the unacceptable on-target, off-tumor effects of other targets expressed in vital tissues.
In Specific Aim 1, we will demonstrate the effectiveness and specificity of targeting OR2H1+ PDX with
CAR T cells in vivo. These studies will support a rationale for subsequent IND approval for OR2H1 CAR T cell
administration in patients with tumors expressing OR2H1 at variable levels.
 In Specific Aim 2, we will define the superiority of XBP1-ablated OR2H1 CAR T cells. These studies will
support a rationale for genetic engineering of OR2H1 CAR T cells, to empower them to resist metabolic
restrictions and inhibitory signals at tumor beds.
In Specific Aim 3, we will optimize a method to identify eligible patients for OR2H1 CAR T cell targeting.
 Our work could exert a profound effect in the field by supporting a first-in-human clinical trial using OR2H1-
targeted CAR T cells against a variety of solid human tumors, which could have significant benefits in a broad
range of cancer patients, with limited or negligible toxicity.

## Key facts

- **NIH application ID:** 10896142
- **Project number:** 5R21CA276205-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jose R Conejo-Garcia
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $213,852
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896142

## Citation

> US National Institutes of Health, RePORTER application 10896142, OR2H1 is an effective target for CAR T cells in human epithelial tumors (5R21CA276205-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10896142. Licensed CC0.

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