Nanobody-ctla4 fusion therapy targeting autoreactive dendritic cells in canine SLE
A novel immunotherapy approach for canine systemic lupus erythematosus that uses TCR-like nanobodies fused to CTLA4-Ig to selectively target self-antigen bearing dendritic cells. This targeted strategy aims to induce antigen-specific immune tolerance while preserving overall T-cell function, offering a precision alternative to broad immunosuppression.
Overview
This research proposes a precision immunotherapy for canine systemic lupus erythematosus (SLE) that selectively targets autoreactive dendritic cells (DCs) responsible for driving autoimmune progression. The approach combines TCR-like nanobodies with a CTLA4-Ig fusion protein to deliver tolerogenic signals specifically to DCs presenting self-antigens. By focusing immune modulation on the disease-driving cell population, the therapy aims to induce antigen-specific tolerance to SLE-associated peptides while preserving global T-cell function—a significant improvement over broad immunosuppressive treatments currently used in veterinary autoimmune disease management.
Technical specifications
Core technology:
- TCR-like nanobody platform engineered to recognize self-antigen bearing dendritic cells
- CTLA4-Ig fusion component that blocks co-stimulatory CD80/CD86-CD28 interactions, inhibiting DC activation
- Yeast display library system for selecting nanobodies with desirable VHH domains against self-antigen targets
- Standard ELISA-based screening protocols for nanobody selection
Mechanism of action:
The fusion construct simultaneously binds self-antigen presenting DCs and delivers CTLA4-Ig mediated inhibitory signals. This dual functionality is designed to promote Treg expansion and tolerance development to specific SLE peptides, rather than causing systemic immunosuppression.
Validation pipeline:
- Cloning of complementarity determining regions from autoreactive TCRs into existing nanobody scaffolds
- Yeast library screening and ELISA-based selection of optimal nanobody candidates
- Fusion of selected nanobodies with CTLA4-Ig
- Safety testing in animal models through established collaborator networks
Technology readiness level
This research is at an early preclinical stage. The underlying nanobody generation pipeline is established and operational, and the scientific rationale is supported by prior murine studies demonstrating that CTLA-4 Ig treatment of DCs followed by adoptive transfer results in antigen-specific Treg expansion. The next phase involves constructing and screening TCR-like nanobody-CTLA4-Ig fusion candidates, followed by safety evaluation in animal models. The technology has not yet entered formal efficacy or clinical trials for canine SLE.
About Oregon State University
Oregon State University is a comprehensive public research university and Oregon’s land‑grant institution, with a main campus in Corvallis and a statewide footprint. Industry partners tap a statewide Extension network and county offices to pilot and scale solutions with communities and companies across Oregon. A coastal marine science campus in Newport anchors ocean research and provides access to open‑ocean wave‑energy test ranges and grid‑connected infrastructure under development nearby, enabling sea‑to‑shore prototyping. Field stations and university‑managed research forests support long‑term trials and product validation in real‑world environments. A dedicated technology transfer office and the OSU Advantage programs—including the Advantage Accelerator—streamline IP, licensing, startup formation, and industry agreements.
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