Innovative Bispecific Nanobody Targeting ALB and MS4A1 for Advanced Cancer Therapy
VHH-P755 is a humanized nanobody-based therapeutic candidate designed to simultaneously target albumin (ALB) and membrane spanning 4-domains A1 (MS4A1). Developed for oncological applications, this construct is currently in Biological Testing, offering a novel approach to cancer treatment. By engaging both ALB and MS4A1, VHH-P755 leverages unique biological mechanisms to optimize pharmacokinetics and tumor targeting. The project encapsulates the latest advances in nanobody engineering, positioning VHH-P755 as a next-generation modality with significant clinical promise against a range of cancers.
| Candidate | VHH-P755 |
| Target | albumin (ALB) membrane spanning 4-domains A1 (MS4A1) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P755 is available for out-licensing and strategic partnerships. We welcome collaboration opportunities with industry partners to accelerate clinical development and maximize the therapeutic and commercial potential of this novel nanobody construct.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P755 |
Modality
VHH-P755 features an advanced half-life extended bispecific format, comprising a humanized single variable domain nanobody with an E1D mutation targeting human CD20, fused by a 35GS linker to a llama nanobody recognizing the T cell receptor. This construct is further coupled to an albumin-binding nanobody, also via a 35GS linker, and is expressed in Pichia pastoris. The modular, single-domain nanobody structure grants VHH-P755 several key advantages: exceptional stability, high tissue penetration, and a small molecular footprint. These properties enable enhanced access to tumor microenvironments and demonstration of sustained action, addressing core challenges in effective cancer therapy.
Target
ALB and MS4A1 are pivotal molecular targets within the context of cancer therapy. ALB, as a major serum protein, is involved in drug transport and extending the systemic half-life of therapeutics. MS4A1, a cell surface marker largely found on B lymphocytes, plays a crucial role in immune regulation and is frequently used in oncology as a marker of certain hematological malignancies. ALB is highly expressed in the circulatory system, whereas MS4A1 is predominantly present on normal and malignant B cells. Targeting ALB enhances pharmacokinetics, while targeting MS4A1 enables selective engagement with cancerous cells. The dual-targeting profile of VHH-P755 incorporates ALB and MS4A1 to maximize tumor targeting, increase therapeutic exposure, and optimize anti-tumor selectivity, making this approach highly strategic and commercially valuable.
Mechanism of Action
VHH-P755 acts through a dual mechanism, engaging both ALB and MS4A1 to address cancer. By targeting ALB, the nanobody construct leverages albumin’s natural longevity in circulation, resulting in extended serum half-life and improved biodistribution. Simultaneously, through MS4A1 targeting, VHH-P755 binds specifically to cancerous B cells expressing this marker, promoting enhanced tumor cell recognition. This multi-targeting mechanism may induce immune-mediated clearance of malignant cells and facilitate the delivery of cytotoxic payloads if further developed into modalities such as ADCs or bispecific T cell engagers. The versatile nanobody platform allows for future adaptation and expanded utility in various oncological contexts.
Cancer
Cancer remains one of the most significant global health challenges, encompassing a diverse array of diseases characterized by uncontrolled cell growth. It poses a substantial burden on healthcare systems worldwide, affecting millions annually across all age groups. Current standard treatments include surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapies. However, many of these modalities face limitations, such as non-specific toxicity, resistance development, and suboptimal tumor selectivity. There is a critical unmet medical need for safer, more effective therapeutics that can overcome resistance mechanisms and improve patient outcomes. VHH-P755 addresses this gap by offering a highly selective, bispecific mechanism that could enhance therapeutic efficacy while potentially reducing systemic side effects. Its nanobody-based format provides additional advantages for tumor targeting and pharmacological optimization, highlighting its promise for future cancer care.