Novel Nanobody Therapeutic Targeting ALB and US28 for the Treatment of Glioblastoma
VHH-P720 is a fully humanized nanobody designed to target both albumin (ALB) and the envelope protein US28 (US28), representing a unique dual-targeting approach for the potential treatment of glioblastoma. Developed as a half-life extended (HLE), trivalent antibody construct, VHH-P720 combines the binding specificity of camelid-derived single domain antibodies with a domain that interacts with human albumin. Expressed in Pichia pastoris strain XL-33 cells, VHH-P720 is currently in the Biological Testing development phase and aims to address critical unmet medical needs in glioblastoma by engaging biologically relevant targets, albumin (ALB) and envelope protein US28 (US28).
| Candidate | VHH-P720 |
| Target | albumin (ALB) Envelope protein US28 (US28) |
| Modality | humanized bispecific VHH |
| Indication | Glioblastoma |
Licensing Opportunity
VHH-P720 is actively open for out-licensing opportunities and collaborative development partnerships. We welcome inquiries from industry partners seeking innovative therapeutics in the area of glioblastoma and targeted nanobody development.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P720 |
Modality
VHH-P720 utilizes a half-life extended, trivalent nanobody architecture, featuring two camelid-derived single domain antibodies targeting US28 and an additional albumin-binding VHH domain. Nanobodies, due to their small molecular size and single domain structure, often demonstrate superior tissue penetration, enhanced stability, and reduced immunogenicity compared to conventional antibodies. The half-life extension conferred by albumin binding maximizes systemic exposure, while the trivalency enables simultaneous targeting of glioblastoma’s relevant molecular pathways. Expression in Pichia pastoris supports scalable, cost-effective manufacturing. These modality advantages render VHH-P720 especially promising for reaching and retaining activity within the tumor microenvironment of glioblastoma.
Target
ALB and US28 are central to the biological activity of VHH-P720. ALB is a highly abundant plasma protein, essential for molecular transport and regulation of osmotic pressure, and is prominently expressed in circulation. US28, a viral G protein-coupled receptor encoded by cytomegalovirus, has been implicated in glioblastoma progression due to its constitutive signaling and association with tumor microenvironment modulation. ALB targeting allows for extended serum half-life, enhancing pharmacokinetics and drug delivery. US28 is frequently expressed in glioblastoma tissues and is recognized for driving cellular proliferation and immune evasion. Thus, ALB and US28 are strategically valuable as dual targets, supporting the innovation and therapeutic potential of VHH-P720 in glioblastoma management.
Mechanism of Action
VHH-P720 functions by simultaneously binding ALB and US28 using its highly specific VHH domains. The anti-ALB component prolongs systemic exposure, taking advantage of albumin’s natural abundance and half-life extension properties. Concurrently, the US28-targeting domains engage the viral GPCR homolog present in glioblastoma, potentially interfering with signaling pathways that support tumor growth and survival. This dual-action approach may disrupt tumor-promoting environments while maintaining high therapeutic concentrations. Furthermore, the nanobody platform offers modular capabilities that could be leveraged to generate antibody-drug conjugates (ADCs), bispecific formats, or immune cell engagers for expanded therapeutic strategies against glioblastoma and other indications.
Glioblastoma
Glioblastoma is one of the most aggressive forms of brain cancer, characterized by rapid growth, diffuse infiltration, and resistance to conventional therapies. It accounts for a significant proportion of primary malignant brain tumors diagnosed globally. Current treatment regimens typically include maximal surgical resection, radiotherapy, and chemotherapy; however, prognosis remains poor due to recurrence and limited therapeutic response. Molecularly targeted therapies are in ongoing development, yet most patients still face significant challenges such as treatment resistance, tumor heterogeneity, and limited blood-brain barrier penetration. There is an urgent, unmet medical need for more effective and durable therapy options. VHH-P720 offers a novel mechanism by dual-targeting ALB for half-life extension and US28 for direct tumor engagement, thereby holding promise for improved therapeutic outcomes in glioblastoma.