Innovative Bispecific Nanobody Targeting CD3 Complex and MUC17 for Stomach Cancer Immunotherapy
VHH-P353 is an advanced humanized nanobody-based bispecific antibody currently in the biological testing stage, developed for the treatment of stomach cancer. This molecule simultaneously targets the CD3 Complex (T Cell Receptor Complex) on T cells and mucin 17, cell surface associated (MUC17), a protein often upregulated in gastric malignancies. By integrating these two specificities within a single construct, VHH-P353 is designed to engage immune effector cells while selectively recognizing tumor-associated MUC17, providing a promising, targeted immunotherapeutic approach for stomach cancer.
| Candidate | VHH-P353 |
| Target | CD3 Complex (T Cell Receptor Complex) mucin 17, cell surface associated (MUC17) |
| Modality | humanized bispecific VHH |
| Indication | Stomach Cancer |
Licensing Opportunity
VHH-P353 is available for out-licensing to partners interested in advancing innovative immunotherapies for oncology. We welcome collaboration and strategic alliances to accelerate its development and commercialization.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P353 |
Modality
VHH-P353 employs a bispecific modality, consisting of a humanized antigen-binding fragment specific to CD3, combined with an anti-MUC17 humanized nanobody domain. Both domains are fused to engineered Fc regions incorporating knob-into-hole and other stabilizing mutations, expressed in human embryonic kidney cells. The use of a nanobody confers unique attributes such as low molecular weight, high stability, and superior tissue penetration compared to conventional antibodies. These properties enable VHH-P353 to efficiently access and interact with tumor sites in stomach cancer, while the bispecific architecture facilitates redirection of immune cells for enhanced antitumor activity.
Target
CD3 Complex is a critical component of the T cell receptor pathway, orchestrating T cell activation and signal transduction in immune responses. It is primarily expressed on the surface of mature T lymphocytes. MUC17, a membrane-associated mucin, is mainly found on epithelial surfaces in the gastrointestinal tract and is increasingly recognized for its overexpression in certain gastric cancers. Both CD3 Complex and MUC17 serve as strategic targets in stomach cancer: CD3 Complex enables redirection of the host’s immune system, while tumor-specific MUC17 provides selective targeting of malignant cells. VHH-P353’s dual engagement of CD3 Complex and MUC17 holds high strategic value for stomach cancer therapeutics, aiming for precision tumor killing with minimized off-target effects.
Mechanism of Action
VHH-P353 exerts its effect through precise, simultaneous targeting of CD3 Complex on T cells and MUC17 on tumor cells. Engagement with the CD3 Complex activates and recruits T lymphocytes, while binding to MUC17 on the tumor surface brings the immune cells into close proximity with cancer cells. This bridging effect enables potent immunological synapse formation and directed cytotoxicity against MUC17-positive stomach cancer cells. Leveraging the signal transduction modulator function, VHH-P353 embodies the growing trend of bispecific and nanobody therapeutics, offering a platform adaptable for further expansion into formats such as antibody-drug conjugates or multi-specific agents targeting solid tumors.
Stomach Cancer
Stomach cancer is a major global health concern, ranking among the leading causes of cancer morbidity and mortality worldwide. Its incidence is particularly high in East Asia and several developing regions. Current management strategies combine surgery, chemotherapy, radiation therapy, and targeted therapies, yet five-year survival remains suboptimal, especially in advanced cases. Limitations of existing treatments include drug resistance, systemic toxicity, and insufficient selectivity for cancer cells. Accordingly, there is a substantial unmet clinical need for more effective, targeted, and safer therapies. By leveraging dual targeting of CD3 Complex and MUC17, VHH-P353 offers the potential to simultaneously harness the immune response and achieve tumor-specific recognition. This approach may overcome key obstacles in the treatment of stomach cancer and represent a next-generation therapeutic innovation.