CD200-Antigen Fusion Proteins For Myeloid-Targeted Antigen-Specific Immune Tolerance

SUMMARY

CD200-antigen fusion proteins target myeloid cells to deliver inhibitory CD200R signals, enhancing antigen uptake and presentation while dampening inflammation to induce antigen-specific immune tolerance

The Unmet Need: Antigen-specific therapies for tolerance induction with mitigated immune activation risk

• Antigen-specific immune tolerance therapies aim to selectively modulate undesired immune responses without broadly suppressing immunity. Conditions such as autoimmune diseases, allergies, and anti‐drug antibody formation cause tissue damage or loss of therapeutic efficacy. Conventional immunosuppressants blunt multiple arms of the immune system, increasing risk of infections and malignancies. Emerging strategies focus on directing antigens to immune regulatory pathways, particularly within myeloid cell populations, to retrain tolerance. Achieving precise delivery of relevant epitopes to inhibitory receptors could enable durable antigen‐specific unresponsiveness while preserving protective immunity, addressing a critical unmet need.

• However, current antigen‐specific approaches face several limitations. Broad immunosuppression increases infection risk, while many targeted delivery systems lack sufficient cell‐type selectivity or induce off‐target activation. Nanoparticle and ex vivo dendritic cell loading protocols are complex and costly, limiting scalability. Glycosylation or glycopolymer‐based antigen carriers often exhibit poor uptake or require high doses. Additionally, most strategies fail to achieve tolerance in the context of active inflammation, as inflammatory cues can override inhibitory signals. These challenges underline the need for more efficient, non‐inflammatory myeloid targeting methods.

The Proposed Solution: Novel method for inducing antigen-specific tolerance by fusing the extracellular domain of CD200 to an antigen of interest- targeting cells with the myeloid-restricted inhibitory receptor CD200R

• The faculty inventor employed fusion proteins linking the extracellular domain of CD200 to specific antigens, directing antigens to CD200R-expressing myeloid cells. Engagement of CD200R delivers inhibitory signals, reducing co-stimulatory receptor expression and inflammatory cytokine release from dendritic cells and other antigen-presenting cells. By harnessing the naturally tolerogenic CD200–CD200R axis, this platform enhances antigen uptake and presentation while limiting immune activation, effectively promoting antigen-specific tolerance even during ongoing immune responses.

• Unlike broad immunosuppressants that compromise host defense, this method exploits a non-inflammatory checkpoint pathway to achieve selective tolerance, avoiding unintended immune activation associated with other myeloid-targeting strategies. Its dual functionality—precise antigen delivery combined with inhibitory signaling—differentiates it from erythrocyte-targeting, glycopolymer-based platforms, nanomaterials, and ex vivo dendritic cell loading. Preclinical models demonstrate superior suppression of antigen-specific T cell responses and induction of anergic phenotypes without systemic immunosuppression, highlighting its potential for tailored therapies in autoimmunity, allergies, and anti-drug immunity.

ADVANTAGES

ADVANTAGES

• Induces antigen-specific immune tolerance without broad immunosuppression

• Targets the non-inflammatory CD200R pathway to avoid unintended immune activation

• Enhances antigen uptake and presentation by myeloid cells

• Downregulates co-stimulatory receptors and inflammatory cytokine release

• Demonstrates efficacy even during active immune responses

APPLICATIONS

• Autoimmune disease tolerance therapy

• Allergy-specific immunotherapy treatment

• Biologic drug immunogenicity suppression

• Inflammatory disease tolerance induction