# Engineering a unique antibody for patients with RA

> **NIH NIH R41** · ABWIZ BIO, INC. · 2021 · $300,000

## Abstract

RA is one of the most common chronic autoimmune disorders that can lead to complete joint
destruction and severe disability if untreated. There is no cure for RA and up to 50% of RA patients do not
respond to anti-TNF therapies as circulating Th-17/IL-17 levels are highly elevated subsequent to TNF
blockade. For this subset of RA patients, disruption of a novel pathway that impairs the synergy between TNF
(M1 macrophages) and IL-17 (Th-17 cells) cascades may resolve the critical barrier in RA treatment. Hence
objective of this project is to develop a therapeutic human TLR5 antibody (Ab) for RA patients whose disease
is driven by the cross-talk between the effector macrophages and T cells.
 We documented that ligation of TLR5 to its natural ligand expressed in the joints, transforms RA
peripheral blood (PB) cells into proinflammatory M1 macrophages which produce high levels of TNF, IL-1 and
IL-6. In addition, IL-6 produced from TLR5 driven M1 macrophages can differentiate the naïve T cells into
inflammatory RA TH-17 cells that secrete IL-17A, IL-17F, IL-22, IL-24, IL-26, CCL20 and GM-CSF. In mice,
systemic and local injection of a TLR5 agonist exacerbates joint swelling; conversely anti-TLR5 Ab treatment
alleviates collagen induced arthritis (CIA) joint inflammation.
 To investigate the role of TLR5 Ab as a potential treatment for RA, we have partnered with scientists at
Abwiz Inc. Using a TLR5 antigen, a human fragment antigen-binding (Fab) phage display library was screened
for TLR5 high affinity binders. Up to 40 positive clones were sequenced and 10 selected TLR5 Fab clones
were expressed, purified and assessed by ELISA for TLR5 binding and cross reactivity. Ten Fab clones were
examined by the Shahrara lab for TLR5 neutralization capacity in human and murine cells and one was
selected based on its superior blocking capacity.
 The overall goal of this project is to develop an anti-TLR5 Ab for RA therapy. In Phase I, our approach
is to enhance the affinity of anti-TLR5 Ab in order to reach a Kd value that is within the range of commercially
available Abs. Candidates provided through site directed mutagenesis using phage-display Ab library, will be
tested for their TLR5 blocking affinity in human cells. Subsequently, the most promising candidates will be
tested for their ability to abrogate RA synovial fluid from promoting inflammatory response in humanized RA
mouse model. The long term goal of this project is to generate a safe and completely novel TLR5 Ab for RA
patients that do not respond to the current therapies.

## Key facts

- **NIH application ID:** 10146288
- **Project number:** 5R41AI147697-02
- **Recipient organization:** ABWIZ BIO, INC.
- **Principal Investigator:** Toshiaki Maruyama
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2020-04-16 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146288

## Citation

> US National Institutes of Health, RePORTER application 10146288, Engineering a unique antibody for patients with RA (5R41AI147697-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146288. Licensed CC0.

---

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