Innovative Bispecific Nanobody Targeting CD3 Complex and CD105 for Next-Generation Cancer Immunotherapy
VHH-P376 is a highly specialized humanized nanobody therapeutic currently in the Biological Testing phase, developed for cancer treatment. This program harnesses a bispecific approach, enabling simultaneous targeting of the CD3 Complex (T Cell Receptor Complex) and endoglin (ENG). By binding to both crucial immune and tumor-associated antigens, VHH-P376 holds the potential to revolutionize cancer immunotherapy by selectively engaging cytotoxic T cells with malignant cells. The unique structure and biological targeting capability of VHH-P376 position it as a promising candidate in the next wave of precision oncology therapeutics.
| Candidate | VHH-P376 |
| Target | CD3 Complex (T Cell Receptor Complex) endoglin (ENG) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P376 is now available for out-licensing opportunities. We invite inquiries from partners interested in collaboration, co-development, or commercialization of this advanced bispecific nanobody program for cancer immunotherapy.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P376 |
Modality
VHH-P376 is designed as a bispecific T-cell engager, composed of two single-domain antibodies (nanobodies)—one directed at CD105 and the other at CD3—joined via flexible G4S linkers. These nanobodies are characterized by their small molecular size, robust folding, and exceptional tissue permeability compared to conventional antibodies. Expressed in Escherichia coli Rosetta cells, VHH-P376 benefits from efficient production and reliable consistency. The compact structure of nanobodies grants VHH-P376 an improved ability to penetrate dense tumor tissue and to access challenging epitopes, potentially translating into more effective tumor targeting and immune synapse formation in cancer therapy.
Target
CD3 Complex and CD105 are integral targets in cancer immunotherapy. The CD3 Complex is a multi-subunit protein found on the surface of T cells and orchestrates the initiation of adaptive immune responses through T cell activation. CD105, also known as endoglin, is a membrane glycoprotein predominantly expressed on proliferating endothelial cells within the tumor microenvironment. CD3 Complex is critical for T cell-mediated cytotoxicity, while CD105 marks newly formed vasculature in growing tumors. By targeting both CD3 Complex and CD105, VHH-P376 leverages the dual strategy of directly engaging cytotoxic T cells and honing in on angiogenic tumor vasculature. The bispecific approach enhances tumor specificity and minimizes potential off-target effects, positioning VHH-P376 as a strategic asset in the immuno-oncology landscape.
Mechanism of Action
VHH-P376 exerts its anti-tumor activity via a bispecific mechanism, binding to CD3 Complex on T cells and CD105 on tumor-associated endothelial cells. This dual engagement brings cytotoxic T lymphocytes into close proximity with the tumor microenvironment, facilitating targeted immune synapse formation and potent T cell activation at the tumor site. By bridging immune effector cells with angiogenic vasculature, VHH-P376 amplifies anti-tumor immunity and may disrupt tumor blood supply. The nanobody platform underlying VHH-P376 is versatile, supporting further engineering into antibody-drug conjugates or other bispecific constructs, thereby broadening potential therapeutic applications and offering expanded value in precision immuno-oncology.
Cancer
Cancer represents a diverse group of diseases characterized by the uncontrolled proliferation and spread of abnormal cells. It remains one of the leading causes of morbidity and mortality worldwide, with millions of new diagnoses annually across various malignancy types. Conventional therapies for cancer include surgery, chemotherapy, radiation, hormonal therapy, targeted agents, and immunotherapies. Despite advances, resistance, off-target toxicity, and heterogeneous tumor biology result in suboptimal outcomes for a significant proportion of patients. There remain pressing unmet medical needs, particularly for tumors with high relapse rates or limited response to established treatments. VHH-P376’s bispecific mechanism facilitates precise immune targeting and vascular disruption within the tumor, offering a promising approach for improved efficacy and safety over traditional modalities. Its development addresses critical gaps in current oncology treatment by harnessing the immune system’s potential with refined tumor specificity.