Innovative Bispecific Nanobody Targeting CD80 and CTLA4 for Autoimmune Disease Therapy
VHH-P574 is a novel humanized nanobody-based therapeutic candidate designed to target both CD80 molecule (CD80) and cytotoxic T-lymphocyte associated protein 4 (CTLA4). Developed as a bispecific construct, VHH-P574 leverages next-generation antibody engineering to simultaneously engage key immune regulatory pathways. Currently in the Biological Testing phase, this program presents significant potential for the treatment of autoimmune disease by modulating immune checkpoint signaling. Its dual-targeting mechanism is intended to restore immune balance, addressing a significant unmet medical need in the management of complex autoimmune conditions.
| Candidate | VHH-P574 |
| Target | CD80 molecule (CD80) cytotoxic T-lymphocyte associated protein 4 (CTLA4) |
| Modality | humanized bispecific VHH |
| Indication | Autoimmune Disease |
Licensing Opportunity
VHH-P574 is available for out-licensing and partnership opportunities. We welcome collaborations with industry partners interested in co-development, commercialization, or further clinical evaluation of this innovative bispecific nanobody program.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P574 |
Modality
VHH-P574 features a bispecific nanobody construct, in which humanized single-domain antibodies against CD80 and CTLA4 are connected via a flexible (G4S)2 linker, and expressed in human embryonic kidney Expi293F cells. Nanobodies possess unique structural characteristics, including small molecular size and single-domain configuration, enabling superior tissue penetration, high stability, and efficient production in eukaryotic systems. These advantages are especially relevant for autoimmune disease, where tissue targeting and modulatory precision are critical. The bispecific design of VHH-P574 allows for simultaneous blockade of two key immune checkpoints, positioning it as a next-generation solution for complex immunological disorders.
Target
CD80 and CTLA4 are immune regulatory proteins playing central roles in T cell activation and immune homeostasis. CD80, a cell surface molecule, and CTLA4, an inhibitory receptor, are primarily expressed on antigen-presenting cells and activated T cells, respectively. Dysregulation of the CD80–CTLA4 pathway is implicated in the pathogenesis of autoimmune disease, as aberrant costimulatory signaling can lead to persistent T cell activation and tissue damage. Targeting CD80 and CTLA4 has been widely validated as an effective strategy for modulating immune tolerance and controlling pathological immune responses. VHH-P574’s bispecific engagement of both CD80 and CTLA4 offers a strategic therapeutic asset, with the potential to finely tune immune cell function and address critical gaps in current autoimmune disease management.
Mechanism of Action
VHH-P574 exerts its therapeutic action by simultaneously binding to CD80 and CTLA4, key regulators of immune checkpoint pathways. By inhibiting CD80 interaction with CD28 and blocking CTLA4-mediated negative signaling, it modulates the activation threshold of T lymphocytes. This dual blockade seeks to restore balance within the immune system, suppressing abnormal autoreactivity while preserving protective immunity. Leveraging the nanobody platform, VHH-P574 offers exceptional modularity, enabling future development of additional bispecifics, antibody-drug conjugates, or multispecific formats. The flexibility and specificity of this approach underline its potential for broad and customizable immune modulation in diverse autoimmune disease contexts.
Autoimmune Disease
Autoimmune diseases encompass a diverse group of chronic disorders characterized by the immune system's inappropriate attack on the body’s own tissues. Globally, millions of individuals are affected by conditions such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. Current therapeutic strategies include immunosuppressants, biologics targeting inflammatory pathways, and immune checkpoint modulators. Despite advances, many patients experience suboptimal response rates, significant adverse effects, and risk of long-term immune compromise. There remains a substantial need for innovative therapies with improved efficacy, safety, and mechanism-driven selectivity. VHH-P574’s bispecific nanobody approach, targeting both CD80 and CTLA4, represents a promising solution—offering precise immune regulation and the potential to achieve durable disease control in patients with refractory or inadequately managed autoimmune diseases.