Bispecific Nanobody Targeting ITGB1 and KCNH2 for Innovative Cancer Therapy
VHH-P735 is a humanized nanobody-based therapeutic agent currently in the Biological Testing phase, specifically designed to treat cancer. This novel candidate is engineered to simultaneously target integrin subunit beta 1 (ITGB1) and potassium voltage-gated channel subfamily H member 2 (KCNH2), both of which are clinically validated targets implicated in tumor progression and metastasis. By engaging these two critical cancer-associated proteins, VHH-P735 offers the potential to disrupt multiple cancer growth pathways, providing a strong rationale for development as a therapeutic option for diverse cancer types.
| Candidate | VHH-P735 |
| Target | integrin subunit beta 1 (ITGB1) potassium voltage-gated channel subfamily H member 2 (KCNH2) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P735 is currently available for out-licensing opportunities. We welcome inquiries from partners interested in co-development, commercialization, or further clinical evaluation of this promising bispecific nanobody cancer therapy.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P735 |
Modality
VHH-P735 is a bispecific nanobody composed of two single-chain diabodies, each directed against ITGB1 and KCNH2. The molecule is constructed as a small, single-domain antibody format, linked by a flexible peptide and strategically engineered with an F95C mutation in the variable domain for enhanced stability and function. Expressed in Pichia pastoris, this modular structure grants increased tissue penetration and exceptional stability, making it highly suitable for targeting solid tumors and challenging microenvironments. The compact size and robust nature of the nanobody modality offer clinical advantages, including enhanced tumor infiltration and the potential for flexible engineering as combination or multi-functional therapies in cancer treatment.
Target
ITGB1 and KCNH2 are two critical molecular targets in oncology. ITGB1 is a cell surface receptor involved in cell adhesion, migration, and signal transduction, primarily expressed on various cancer cell types as well as in the tumor microenvironment. KCNH2 is a potassium channel with roles in cellular signaling and proliferation, found in both normal and malignant tissues, but often upregulated in multiple cancer types. Both ITGB1 and KCNH2 have been linked to enhanced tumor growth, metastasis, and poor clinical outcomes. By directly targeting ITGB1 and KCNH2, VHH-P735 is strategically positioned to disrupt important cancer survival pathways, providing a dual mechanism that distinguishes it from monospecific agents and increasing its potential therapeutic value in a range of cancers.
Mechanism of Action
VHH-P735 operates via dual blockade of ITGB1 and KCNH2, leveraging its bispecific nanobody architecture to achieve coordinated modulation of tumor cell signaling. By binding to ITGB1, VHH-P735 can inhibit pathways governing cell adhesion, invasion, and migration, potentially preventing metastasis. Simultaneously, antagonism of KCNH2 interferes with tumor cell proliferation and survival pathways regulated by potassium channel activity. Combined, these mechanisms produce synergistic anti-tumor effects. The nanobody platform underlying VHH-P735 also enables further therapeutic innovations, such as adaptation into antibody-drug conjugates (ADC) or development of multi-specific agents, broadening its application potential in oncology pipelines.
Cancer
Cancer remains a leading global health challenge, affecting millions of individuals annually and representing a major cause of morbidity and mortality worldwide. The disease encompasses a heterogeneous group of malignancies, each with distinct genetic, molecular, and clinical features. Current mainstays of treatment include surgery, radiation therapy, chemotherapy, and targeted biological agents, with immunotherapy emerging as a transformative approach in recent years. However, many cancers remain refractory to standard therapies, and the development of resistance, toxicity, and limited tumor specificity continue to constrain clinical outcomes. There remains a critical unmet need for innovative therapies that can address tumor heterogeneity, invasiveness, and relapse. VHH-P735, by targeting both ITGB1 and KCNH2, offers a novel strategy to confront cancer’s complexity and therapy resistance, with the potential to fulfill pressing needs for effective and versatile oncologic treatments.