Bispecific Nanobody Targeting MSLN and TNFRSF17 for Innovative Cancer Immunotherapy
VHH-P651 is a bispecific, fully humanized nanobody currently in the Biological Testing stage, engineered to target both mesothelin (MSLN) and TNF receptor superfamily member 17 (TNFRSF17). This dual-targeting approach aims to address multiple hallmarks of cancer by binding MSLN, a surface protein overexpressed in many solid tumors, and TNFRSF17, frequently found on malignant B cells and implicated in tumor progression. VHH-P651 is designed to improve anti-tumor efficacy and offers a promising pathway in cancer treatment by engaging both tumor-associated and immune-activating targets simultaneously.
| Candidate | VHH-P651 |
| Target | mesothelin (MSLN) TNF receptor superfamily member 17 (TNFRSF17) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P651 is currently available for out-licensing and collaboration opportunities. We welcome inquiries from partners interested in advancing cutting-edge bispecific nanobody therapeutics in the oncology field.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P651 |
Modality
VHH-P651 is a bispecific nanobody consisting of single heavy chain variable domain antibodies that separately target MSLN and TNFRSF17, connected via a flexible (G4S)3 linker. This compact design combines the unique benefits of nanobodies—such as small molecular size, high tissue penetration, and increased stability—enabling deeper tumor infiltration and enhanced biodistribution for cancer therapy. The bispecific configuration supports simultaneous recognition and modulation of distinct cellular targets, potentially increasing therapeutic impact while minimizing off-target effects.
Target
MSLN and TNFRSF17 are critical molecular targets in oncology. MSLN is a cell surface glycoprotein largely restricted to mesothelial cells under normal physiology but highly upregulated in diverse cancers, including mesothelioma, ovarian, and pancreatic tumors. TNFRSF17, a receptor in the tumor necrosis factor superfamily, is mainly expressed on B lymphocytes and is overrepresented in multiple myeloma and certain B-cell malignancies. Targeting MSLN disrupts tumor cell adhesion and invasion, while addressing TNFRSF17 modulates malignant B-cell survival and proliferation. VHH-P651's dual specificity for MSLN and TNFRSF17 positions it as a strategic asset, leveraging the complementary biology of these targets to maximize anti-tumor efficacy while addressing heterogeneity in cancer expression profiles.
Mechanism of Action
VHH-P651 achieves its therapeutic effect through dual antigen engagement: it binds to MSLN on tumor cell surfaces and simultaneously targets TNFRSF17—also referred to as CD269 or BCMA—on malignant cells. By incorporating immune cell activator domains, VHH-P651 is designed to modulate signal transduction pathways, thereby enhancing immune-mediated cytotoxicity against cancer cells. As part of the nanobody platform, this bispecific construct demonstrates the versatile potential for further development, including adaptation into multivalent formats, fusion to cytotoxic payloads for ADC strategies, and expansion to other immune-modulating targets. This mechanism enables a multifaceted intervention, directly antagonizing oncogenic pathways while enlisting the immune system for targeted cancer cell elimination.
Cancer
Cancer remains a leading cause of morbidity and mortality worldwide, encompassing a diverse range of malignant disorders originating from uncontrolled cellular proliferation. It presents a significant healthcare burden, with millions of new cases diagnosed annually across both developed and emerging economies. Standard treatment options include surgical resection, radiotherapy, chemotherapy, immunotherapy, and molecularly targeted agents. Despite recent advances, current approaches often suffer from inadequate specificity, systemic toxicity, treatment resistance, and disease relapse. Particularly in cases expressing MSLN and TNFRSF17, tumor heterogeneity and immune evasion create additional therapeutic challenges. The dual specificity of VHH-P651 is poised to address these unmet needs by precisely targeting both tumor and immune cell antigens, potentially improving therapeutic outcomes and expanding the clinical benefit to patients who may not respond to conventional mono-target therapies.