Next-Generation Bispecific Nanobody Targeting CD3 Complex and EPCAM for Innovative Cancer Immunotherapy
VHH-P561 is an advanced, fully humanized bispecific nanobody designed to simultaneously engage the CD3 Complex (T Cell Receptor Complex) and epithelial cell adhesion molecule (EPCAM). Currently at the Biological Testing stage, this novel molecule leverages the specificity of modular antibody engineering to facilitate potent immune cell redirection for the treatment of cancer. By joining anti-CD3 and anti-EPCAM activities in one compact format, VHH-P561 holds strong therapeutic promise for optimizing targeted cytotoxicity and enhancing cancer immunotherapy outcomes.
| Candidate | VHH-P561 |
| Target | CD3 Complex (T Cell Receptor Complex) epithelial cell adhesion molecule (EPCAM) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P561 is available for out-licensing and strategic partnerships. We welcome collaborations with biopharmaceutical companies and research organizations interested in advancing this innovative bispecific nanobody program for cancer immunotherapy.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P561 |
Modality
VHH-P561 is a bispecific antibody construct featuring an anti-EPCAM nanobody fused to both the N-terminus of the heavy and light chains of an anti-CD3 monoclonal IgG1, utilizing a flexible GSGGGGS linker. The nanobody component, characterized by its small size and single variable domain structure, enables superior tissue penetration and stability compared to conventional antibodies. Mutations in the Fc region (P329G, L234A, L235A) serve to modulate effector functions, optimizing safety and efficacy for cancer therapy. This innovative design allows for precise engagement of tumor and immune cells, maximizing anti-cancer potential while minimizing systemic immune activation.
Target
CD3 Complex and EPCAM are pivotal molecular targets for cancer immunotherapy. CD3 Complex is a cell surface protein complex expressed primarily on T cells and is crucial for T-cell activation and signal transduction. EPCAM is a glycoprotein widely expressed on epithelial cells and is frequently overexpressed in diverse epithelial-derived cancers. Targeting CD3 Complex enables potent T-cell recruitment, while EPCAM targeting ensures selective engagement with tumor cells. The combined dual specificity for CD3 Complex and EPCAM in VHH-P561 allows for strategic bridging of immune and tumor cells, fostering effective cytotoxic synapse formation. Harnessing both CD3 Complex and EPCAM as therapeutic touchpoints underpins the innovation and potential superiority of VHH-P561 among next-generation immune engager therapies for cancer.
Mechanism of Action
VHH-P561 exerts its anti-cancer effect as a T-cell engager by simultaneously binding to CD3 Complex on T cells and EPCAM on tumor cells. This dual binding brings cytotoxic T lymphocytes into close proximity with EPCAM-expressing cancer cells, facilitating targeted T-cell activation and tumor cell lysis. The bispecific nanobody structure optimizes immune synapse formation, while the engineered Fc region minimizes undesirable immune activation, supporting a favorable safety profile. Additionally, the modularity of the nanobody platform offers future opportunities for engineering related immunotherapeutic formats—including antibody-drug conjugates or multispecific constructs—further expanding therapeutic versatility against cancer.
Cancer
Cancer remains one of the leading causes of morbidity and mortality worldwide, with millions of new cases diagnosed annually across diverse populations. Standard therapies encompass surgery, radiotherapy, chemotherapy, and more recently, targeted agents and immunotherapies. Despite these advancements, drug resistance, off-target effects, and limited immune response remain persistent challenges, contributing to poor prognosis in many cancer types. There is a pressing need for therapies that deliver higher selectivity, reduced systemic toxicity, and durable anti-tumor effects. VHH-P561 addresses these unmet clinical needs by enabling precise, immune cell-mediated targeting of malignant cells overexpressing EPCAM, harnessing T-cell cytotoxicity via CD3 Complex engagement. This novel immunotherapeutic approach has the potential to significantly improve outcomes for cancer patients while expanding treatment possibilities into otherwise refractory disease settings.