Advancing Cancer Therapy with a Bispecific Nanobody Targeting MUC16 and TNFRSF9

VHH-P413 is a humanized nanobody-based bispecific antibody candidate, currently in the Biological Testing phase, designed to target mucin 16, cell surface associated (MUC16) and TNF receptor superfamily member 9 (TNFRSF9). Engineered for the innovative treatment of cancer, VHH-P413 combines the specificity of MUC16 binding with agonistic modulation of TNFRSF9 signaling. Its unique format enables precise targeting of malignant cells expressing MUC16 and potentiates immune activation through TNFRSF9, offering promising therapeutic potential for various cancer indications. This dual targeting strategy positions VHH-P413 as a novel approach with anticipated benefit over conventional monotherapies.

Licensing Opportunity

VHH-P413 is available for out-licensing and collaboration opportunities. We welcome inquiries from partners interested in advancing innovative bispecific nanobody-based immunotherapies for cancer treatment.

Development Phase

Modality

VHH-P413 is a bispecific antibody engineered with a single-domain antibody (nanobody) specific for TNFRSF9 fused to the C-terminus of the heavy chain of an anti-MUC16 IgG1 framework, and a N297A mutation in the Fc region to reduce effector function. The small size and unique structure of the nanobody domain confer superior tissue penetration and increased stability, while the IgG1 scaffold affords prolonged half-life. This multimodal structure allows VHH-P413 to access tumor microenvironments more efficiently, overcoming barriers typical for conventional antibodies, thus potentially enhancing anti-cancer efficacy through optimal target engagement and immune modulation.

Target

MUC16 is a membrane-associated glycoprotein predominantly expressed on the surface of various epithelial cancers, most notably ovarian cancer, while TNFRSF9 is a cell surface receptor belonging to the tumor necrosis factor receptor superfamily, expressed primarily on activated T cells and other immune subsets. Both MUC16 and TNFRSF9 have been validated as strategic targets in cancer: MUC16 is linked to tumor progression, metastasis, and immune evasion, making it an attractive antigen for tumor targeting; TNFRSF9 functions as a potent immune co-stimulatory molecule, amplifying T cell anti-tumor responses. Dual targeting of MUC16 and TNFRSF9 with VHH-P413 harnesses tumor specificity while simultaneously activating anti-cancer immunity, representing a distinctive value proposition for targeted cancer immunotherapy.

Mechanism of Action

VHH-P413 achieves anti-cancer activity by simultaneously binding to MUC16 on tumor cells and acting as an agonist for TNFRSF9 on immune cells. The nanobody module targets TNFRSF9, providing immune costimulation, while the IgG1 backbone confers high-affinity binding to MUC16, ensuring tumor specificity. This dual engagement facilitates the colocalization of immune effector cells with tumor cells, potentiating immune-mediated tumor cell elimination via TNFRSF9-driven activation. The modular design allows for additional engineering capacity, including adaptation into antibody-drug conjugates (ADC) or alternative bispecific and multispecific therapeutic formats, showcasing the broad platform potential of the nanobody strategy for addressing heterogeneous cancer pathologies.

Cancer

Cancer remains one of the leading causes of morbidity and mortality worldwide, affecting millions of individuals across all demographics. Current mainstays of treatment include surgery, chemotherapy, radiotherapy, targeted therapies, and various immunotherapy modalities. Despite significant advances, many patients confront challenges such as recurrence, resistance to standard therapies, and adverse side effects. Targeted immunotherapies, especially those engaging both tumor markers and immune regulatory pathways, represent a scientifically validated approach to overcoming these barriers. VHH-P413 is designed to address key limitations of conventional treatments by providing precise tumor targeting via MUC16 and enhancing immune activation through TNFRSF9 modulation. This dual mechanism offers the potential to improve tumor eradication while minimizing off-target toxicity, aligning with the urgent unmet need for more effective and safer cancer therapies.