Innovative Bispecific Nanobody Targeting CDH17 and CD3 Complex for Pancreas Cancer Immunotherapy

VHH-P796 is a humanized nanobody-based bispecific antibody construct currently in Biological Testing, designed for the potential treatment of pancreas cancer. This molecule incorporates a single-domain antibody arm targeting cadherin 17 (CDH17) extracellular domains and a humanized anti-CD3 VHH arm, fused through a silenced IgG Fc region. By engaging both cadherin 17 (CDH17) and the T Cell Receptor Complex (CD3 Complex), VHH-P796 is engineered to precisely redirect T cell cytotoxicity to cancer cells, aiming to overcome immune evasion in pancreas cancer.

Licensing Opportunity

VHH-P796 is available for out-licensing and collaborative development. We welcome inquiries from partners interested in advancing this innovative bispecific nanobody program in pancreas cancer and immuno-oncology.

Development Phase

Modality

VHH-P796 is constructed as a bispecific T-cell engager antibody, utilizing two humanized single-domain VHHs: one directed against CDH17 and the other against CD3 Complex, both fused to a silenced IgG Fc backbone. The nanobody format offers advantages of compact size, increased tissue penetration, and high stability, making it particularly suitable for targeting dense pancreatic tumor microenvironments. Fusing with a silenced Fc further enhances serum half-life while minimizing non-specific immune activation, supporting an improved safety and efficacy profile for pancreas cancer immunotherapy.

Target

CDH17 and CD3 Complex represent highly relevant targets in advanced immuno-oncology. CDH17 is a transmembrane protein implicated in cellular adhesion and is predominantly overexpressed in various gastrointestinal malignancies, including pancreas cancer, with low expression in most normal tissues. The CD3 Complex is an essential component of the T cell receptor, expressed on all mature T cells and critical for T cell activation. By targeting CDH17 on tumor cells and CD3 Complex on cytotoxic T lymphocytes, VHH-P796 bridges cancer cell recognition with immune effector function. This dual specificity allows for selective tumor cell targeting and potent immune synapse formation, establishing significant strategic value and differentiation for pancreas cancer therapy by harnessing and redirecting the patient’s own immune system.

Mechanism of Action

VHH-P796 acts as a bispecific T-cell engager that binds selectively to CDH17 on pancreatic cancer cells and to CD3 Complex on T cells. This dual engagement brings T cells into proximity with tumor cells, triggering targeted T cell activation and cytotoxicity against CDH17-expressing malignancies. The molecular engineering leverages the high specificity of nanobody regions to minimize off-target effects while maximizing immune synapse formation. This platform also allows potential development of further nanobody-derived modalities, such as antibody-drug conjugates or additional bispecific constructs, expanding its applicability across a range of solid tumors with relevant antigen profiles.

Pancreas Cancer

Pancreas cancer remains one of the most challenging malignancies in oncology, characterized by late diagnosis, aggressive progression, and poor prognosis. While the global incidence continues to rise, the disease represents a leading cause of cancer-related mortality. Current therapeutic approaches include surgical resection, chemotherapy, and, in certain cases, targeted therapies or immunotherapies. However, pancreas cancer is particularly resistant to conventional treatments, with high rates of recurrence and limited survival benefit for most patients. Immunotherapeutic strategies have yet to show consistent breakthroughs, partly due to the immunosuppressive tumor microenvironment and a lack of effective tumor-specific targets. VHH-P796 leverages the overexpression of CDH17 in pancreas cancer and the essential immune-activating function of CD3 Complex, providing a novel approach to redirect immune effector cells specifically toward malignant tissue. This targeted strategy has the potential to address major unmet needs in pancreas cancer treatment by offering improved specificity, efficacy, and the possibility for combination regimens.