Innovative Tri-Specific Nanobody-Driven Cancer Immunotherapy Targeting ANTXR1 and FCGR3A
VHH-P836 is a tri-specific, humanized nanobody therapeutic candidate currently in the Biological Testing stage, developed for the treatment of cancer. This advanced molecule is specifically engineered to target ANTXR cell adhesion molecule 1 (ANTXR1) and Fc gamma receptor IIIa (FCGR3A), two clinically significant markers implicated in tumor progression and immune regulation. By engaging both ANTXR1 and FCGR3A, VHH-P836 is designed to bridge innate immune effector cells and tumor vasculature, offering a novel approach for targeted cancer immunotherapy. The differentiated mechanism and rational target selection position VHH-P836 as a potential best-in-class option for addressing cancer's multifaceted biology.
| Candidate | VHH-P836 |
| Target | ANTXR cell adhesion molecule 1 (ANTXR1) Fc gamma receptor IIIa (FCGR3A) |
| Modality | humanized VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P836 is now available for out-licensing and strategic partnership. We welcome organizations interested in advancing innovative cancer immunotherapies to discuss collaboration and development opportunities.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P836 |
Modality
VHH-P836 features a tri-specific killer cell engager modality, comprising a humanized monoclonal antibody framework that targets CD16, fused to wild-type interleukin-15, and a single-chain variable fragment directed against a tumor endothelial marker. The use of a nanobody structure, characterized by its single-domain configuration and low molecular weight, offers enhanced tumor penetration, improved tissue distribution, and robust biophysical stability. These structural advantages are particularly beneficial for cancer therapy, enabling deeper access into solid tumors and supporting sustained therapeutic activity. The modularity and manufacturability of nanobodies further enhance their versatility for advanced immunotherapeutic applications.
Target
ANTXR1 and FCGR3A are cell-surface proteins with pivotal roles in cancer biology. ANTXR1 is a transmembrane receptor involved in cellular adhesion and angiogenesis, predominantly expressed on tumor endothelial cells and various malignancies. FCGR3A is a receptor expressed mainly on natural killer cells and macrophages, crucial for mediating antibody-dependent cellular cytotoxicity. Targeting ANTXR1 disrupts tumor vasculature and microenvironment support, while FCGR3A engagement leverages innate immune activation. Both ANTXR1 and FCGR3A have been validated as promising targets for innovative cancer therapies. VHH-P836’s dual targeting of ANTXR1 and FCGR3A addresses both tumor compartment and immune effector functions, representing a strategically valuable asset for cancer treatment.
Mechanism of Action
VHH-P836 operates through simultaneous binding to ANTXR1 on tumor endothelial cells and FCGR3A (CD16) on natural killer cells and macrophages. This engagement facilitates immune synapse formation, effectively redirecting cytotoxic effector cells towards tumor vasculature expressing ANTXR1. The embedded wild-type interleukin-15 potentiates immune cell proliferation and activation, amplifying antitumor immune responses. By modulating both signal transduction and cellular interactions, VHH-P836 orchestrates targeted tumor cell clearance while minimizing off-target effects. Leveraging the nanobody platform, this molecule also holds promise for expansion into antibody-drug conjugates or bispecific formats, enabling broad adaptability across oncological settings.
Cancer
Cancer represents a global healthcare challenge, spanning hundreds of subtypes and affecting millions worldwide each year. Characterized by uncontrolled cell growth, invasion, and metastasis, cancer remains the second leading cause of mortality. Current treatment paradigms include surgery, radiotherapy, chemotherapy, immunotherapy, and targeted biological agents; however, many patients face recurrence, drug resistance, and significant side effects due to the heterogeneity of tumors and limited selectivity of present therapies. There is a critical unmet need for more effective, targeted approaches that can harness the body’s immune system while minimizing collateral damage. VHH-P836, with its ability to selectively engage both tumor vasculature (via ANTXR1) and potentiate innate immune attack (through FCGR3A and IL-15), offers the potential to overcome key obstacles in cancer care, with versatility across different tumor types and settings.