# Peptide-HLA-DQ2 biologics for antigen-specific therapy in Celiac Disease

> **NIH NIH R43** · ANTIGER THERAPEUTICS INC. · 2024 · $293,680

## Abstract

PROJECT SUMMARY/ABSTRACT
Antiger Therapeutics Inc is a biotech company specializing in engineering recombinant human leukocyte
antigens (HLA) and membrane proteins. In this SBIR Phase I application, we leverage this expertise to develop
targeted immunotherapies for celiac disease (CD), a global health challenge affecting approximately 100
million individuals. As a chronic autoimmune disease, CD poses serious health risks such as malnutrition,
anemia, reduced bone density, neurological disorders, and cancers like lymphoma. The current paradigm of
CD immunotherapies relies heavily on nonselective immunosuppression, but the associated toxicity limits their
long-term use. The most effective management strategy is a lifelong adherence to a gluten-free diet (GFD).
However, approximately 30% of CD patients experience persistent or recurrent symptoms due to poor dietary
compliance, limited access to GFD, or the complexities of managing refractory CD. Antiger Therapeutics Inc
aims to approach CD therapy by selectively targeting the aberrant immune response. A pivotal immunogenetic
factor in CD is the HLA-DQ2 membrane protein, which presents deamidated gluten peptides to activate
pathogenic T cells and disrupt immune tolerance. Our primary objective is to develop a biologic that specifically
blocks the pathogenic T cells recognizing the gluten peptide-DQ2 (pDQ2) complex, thereby safely preventing
or reversing CD. Because the pDQ2 complex is difficult to assemble due to the inefficient pairing of DQα and
DQβ chains, we will employ novel solutions involving disulfide engineering or producing full-length membrane
proteins. Notably, the disulfide bond approach has shown promise in our recent success in generating stable
pDQ7-Fc molecules for treating antibody-mediated graft rejection. In Specific Aim 1 of this grant, we will
generate dimeric pDQ2-Fc fusion proteins with an inter-chain disulfide bond to stabilize the pDQ2 complex.
The Fc portion enables dimerization of the pDQ2 complex in an antibody-like structure. In Specific Aim 2, we
will generate pDQ2-Transmembrane proteins on detergent micelles. The transmembrane domains of full-
length α and β chains of DQ2 will promote the assembly of pDQ2 complex to be solubilized on micelles. In
both aims, we will assess the yield and purity of multimeric pDQ2 proteins and measure their inhibitory effect
on the activation of pDQ2-specific T cells. By the end of this Phase I SBIR, we expect to generate one or more
candidate proteins with acceptable production yield, purity, and function. The Phase II SBIR will focus on
testing candidate biologics in humanized murine CD models, ultimately leading toward an IND submission.
Commercially, Antiger intends to collaborate with or license the product to a pharmaceutical company for
further development, aiming to tap into the high-demand CD therapeutic market, which is projected to be worth
$3 billion by 2030. Moreover, the scalable technology holds promise for addressing other...

## Key facts

- **NIH application ID:** 11005875
- **Project number:** 1R43AI186651-01
- **Recipient organization:** ANTIGER THERAPEUTICS INC.
- **Principal Investigator:** HONGJIE GUO
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $293,680
- **Award type:** 1
- **Project period:** 2024-06-20 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11005875

## Citation

> US National Institutes of Health, RePORTER application 11005875, Peptide-HLA-DQ2 biologics for antigen-specific therapy in Celiac Disease (1R43AI186651-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11005875. Licensed CC0.

---

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