Innovative Nanobody Targeting ALB and CD274 for Advanced Colorectal Cancer Applications
VHH-P811 is a next-generation therapeutic candidate utilizing a humanized single-domain antibody with specificity for albumin (ALB) and the CD274 molecule (CD274). The construct incorporates a Copper-64 radiolabel for potential diagnostic and therapeutic advantages. Currently in the Biological Testing development stage, VHH-P811 represents a promising approach for the treatment of colorectal cancer, leveraging dual targeting of ALB and CD274 as a differentiated strategy. The inclusion of both albumin and immune checkpoint targeting may address critical pathways associated with tumor progression and immune evasion in colorectal cancer.
| Candidate | VHH-P811 |
| Target | albumin (ALB) CD274 molecule (CD274) |
| Modality | humanized bispecific VHH |
| Indication | Colorectal Cancer |
Licensing Opportunity
VHH-P811 is currently open for out-licensing and partnership opportunities. We welcome collaborations with industry leaders and research organizations aiming to advance innovative therapeutics for colorectal cancer.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P811 |
Modality
VHH-P811 is based on a chemically defined immunoconjugate modality comprising a single-domain nanobody structure with high stability and a compact molecular size. The molecule is engineered with a radiolabeling component (Copper-64), a PD-L1 (CD274) targeting moiety, and a fused albumin-binding domain via a flexible (G4S)3 linker. Expression in CHO cells ensures scalability and efficient production. The single-domain format offers excellent tissue penetration, rapid tumor localization, and favorable pharmacokinetic profiles, which are essential for effective colorectal cancer targeting. Radiolabeling with Copper-64 also opens avenues for real-time imaging and therapeutic applications, enhancing its clinical potential.
Target
VHH-P811 is designed to specifically target both ALB and CD274, two crucial proteins involved in tumor biology and immunity. ALB is the most abundant protein in plasma, frequently used to extend the circulatory half-life of biologics. CD274, also known as PD-L1, is a transmembrane protein expressed on tumor cells and various immune cells; it acts as an immune checkpoint and enables tumors to evade immune surveillance. Both ALB and CD274 are widely expressed in tissues relevant to colorectal cancer progression. Targeting CD274 has become an established approach for immune modulation in the tumor microenvironment, while leveraging ALB interactions can improve bioavailability. Dual targeting of ALB and CD274 represents a strategic innovation in colorectal cancer therapy, offering potential optimization of therapeutic exposure and immune response modulation within the tumor milieu.
Mechanism of Action
VHH-P811 acts via dual targeting of ALB and CD274. By binding to CD274, this nanobody blocks the interaction between PD-L1 and immune checkpoints, thereby reinvigorating anti-tumor immune responses. In parallel, the albumin-binding domain facilitates extended circulation and enhanced accumulation within tumor tissue, thanks to albumin’s natural biodistribution. This combined approach allows VHH-P811 to exert potent immune checkpoint inhibition with improved pharmacokinetics. Furthermore, the nanobody platform is suitable for modular design, offering opportunities to create antibody-drug conjugates, bispecific constructs, or theranostic agents by harnessing similar scaffold and engineering principles.
Colorectal Cancer
Colorectal cancer is a major oncological challenge, ranking among the most common malignancies globally and contributing substantially to cancer-related morbidity and mortality. Standard management includes surgical intervention, chemotherapy, radiotherapy, and targeted biological agents. Despite advances, recurrence and resistance are frequent, and many patients experience suboptimal long-term outcomes due to metastatic spread and immune evasion. Immune checkpoint blockade is emerging as a critical modality, yet current agents may not achieve durable responses in all populations. VHH-P811 has the potential to address these unmet needs by combining targeted immune modulation (via CD274) with albumin-mediated pharmacokinetic enhancement. This innovative approach may offer improved tumor targeting, increased therapeutic efficacy, and the possibility for imaging-guided management strategies in colorectal cancer care.