# Particulate-based in vivo modulation for immunotherapy of Rheumatoid Arthritis

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $330,872

## Abstract

PARTICULATE-BASED IN VIVO MODULATION FOR IMMUNOTHERAPY OF RHEUMATOID ARTHRITIS
PROJECT SUMMARY/ ABSTRACT
 Rheumatoid arthritis (RA) is a chronic, systemic, auto-inflammatory disease that affects approximately 1%
of adults worldwide, and commonly results in joint destruction and significant impairment in the quality of life.
The underlying cause of RA is dendritic cell (DC) activation of antigen-specific T cell subsets in the joints, which
drive inflammatory responses to the synovial membrane that are typically characterized by hyperplasia,
increased vascularity, inflammatory cell infiltration and over production of pro-inflammatory cytokines (particularly
IL-1, IL-6 and TNF-α) by monocytes, macrophages and synovial fibroblasts. Due to their critical role in RA
progression, these cytokines have become the major therapeutic targets for RA therapy. Other therapeutic
approaches include administration of steroids, as well as, anti-angiogenesis drugs. However, these strategies
do not address the root cause of RA – stimulation of T lymphocytes by DCs. A number of factors are known to
promote advantageous dendritic cell responses in experimental systems for autoimmune diseases. However,
systemic delivery of these agents often results in significant harmful off-target effects. The Lewis Lab at UC,
Davis is developing a novel, biomaterial-based, microparticle `anti-vaccine' for in vivo co-delivery of pro-tolerance
factors and autoantigens, targeted to DCs. Exogenous conditioning of DCs with certain immuno-modulatory
agents has been shown to induce a pro-tolerance DC phenotype, as well as, ameliorate RA. However,
vaccination with a microparticle anti-vaccine promises to correct aberrant autoimmune responses, whilst
circumventing problems associated with DC-based cellular therapy such as DC phenotypic stability and
survivability, and autoantigen plurality. The long-term goal is to develop a modular, anti-vaccine system for
autoimmune disease therapy. The overall objective of this R01 proposal is to engineer a multi-component, MP
anti-vaccine to attenuate RA progression in an aggressive, murine RA model, and investigate the extent of
immune modulation following anti-vaccination. The central hypothesis is that this MP anti-vaccine will induce
autoantigen-specific tolerance by targeted delivery of model-relevant autoantigen and tolerance-inducing factors
to immune cells, especially DCs, thereby generating aAg-specific tDCs that will retrain downstream adaptive
responses and promote the remission of RA. This hypothesis will be tested by pursuing four specific aims: 1)
Assess the effect of material properties and anti-vaccine agent presentation on the tolerogenicity of DC
immunotherapy; 2) Evaluate the capacity of this platform system to limit RA in the FIA-CIA mouse model; 3)
Investigate mechanisms of immune tolerance using well-defined antigen-specific mouse models; and 4)
Investigate preliminary manufacturing and safety metrics with an eye towards clinical tra...

## Key facts

- **NIH application ID:** 10676258
- **Project number:** 5R01AI139399-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Jamal S Lewis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $330,872
- **Award type:** 5
- **Project period:** 2019-07-24 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10676258

## Citation

> US National Institutes of Health, RePORTER application 10676258, Particulate-based in vivo modulation for immunotherapy of Rheumatoid Arthritis (5R01AI139399-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10676258. Licensed CC0.

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