Innovative Bispecific Nanobody Targeting FOLR1 and NCR1 for Advanced Cancer Immunotherapy

VHH-P234 is a novel humanized nanobody-based bispecific antibody targeting both folate receptor alpha (FOLR1) and natural cytotoxicity triggering receptor 1 (NCR1). Currently in the Biological Testing stage, this program addresses major therapeutic challenges in cancer. By simultaneously engaging FOLR1, which is overexpressed in many tumor types, and NCR1, a critical receptor on natural killer cells, VHH-P234 is designed to harness and direct the immune response towards malignant cells. Its dual-targeting approach positions it as a promising therapeutic option with the potential to enhance anti-tumor efficacy in a wide array of cancer subtypes.

Licensing Opportunity

VHH-P234 is available for out-licensing and partnership opportunities. We welcome collaborations with industry partners interested in advancing this differentiated bispecific nanobody for cancer therapy. Contact us to discuss co-development or licensing arrangements.

Development Phase

Modality

VHH-P234 utilizes a bispecific modality, combining a camelid single-domain antibody (VHH) targeting FOLR1 with a VHH specific for NCR1, connected via an a3 linker and fused to both arms of a human Fc domain. This design leverages key nanobody advantages: small molecular size for superior tumor tissue penetration, exceptional structural stability, and high solubility. The inclusion of an Fc domain extends serum half-life and promotes immune effector functions, while E. coli-based expression supports scalable, cost-effective production. These features collectively enhance the therapeutic potential of VHH-P234 in cancer by improving tumor accessibility and maintaining robust functional activity.

Target

FOLR1 is a membrane-associated receptor involved in folate transport and cellular proliferation, predominantly expressed on certain epithelial cancer cells. Its limited distribution in normal tissues and frequent overexpression in various tumors make FOLR1 a valuable cancer target. NCR1 is an activating receptor mainly found on natural killer (NK) cells, where it triggers cytotoxic responses against malignant cells. The dual targeting of FOLR1 and NCR1 capitalizes on selective tumor recognition and potentiation of immune-mediated cell killing. Co-targeting FOLR1 and NCR1 with VHH-P234 strategically links antigen-specific tumor engagement with NK cell activation, offering a highly attractive mechanism for next-generation immunotherapies. This dual-targeting approach enhances tumor specificity and holds significant promise for cancer treatment innovation.

Mechanism of Action

VHH-P234 exerts its anti-cancer effects by simultaneously binding to FOLR1 on tumor cells and NCR1 on NK cells. By physically bridging these two cell types, the bispecific nanobody is designed to induce immune synapse formation, thereby facilitating the targeted destruction of FOLR1-expressing cancer cells through NK cell-mediated cytotoxicity. This mechanism bypasses the need for additional antigen presentation or MHC compatibility, potentially expanding clinical utility across diverse patient populations. The nanobody platform of VHH-P234 is amenable to further development, such as integration into antibody-drug conjugates (ADC) or alternative bispecific constructs, providing a versatile foundation for broad oncological applications.

Cancer

Cancer encompasses a spectrum of diseases characterized by uncontrolled cell growth and malignancy. It remains one of the leading causes of morbidity and mortality worldwide. The most prominent therapeutic strategies include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, each with inherent limitations such as toxicity, resistance, or limited selectivity. Despite advances, significant unmet needs persist, particularly in overcoming immune evasion and improving specificity for tumor cells. Emerging modalities like bispecific antibodies, exemplified by VHH-P234, offer novel mechanisms to enhance tumor targeting and immune engagement. By redirecting the cytotoxic activity of NK cells specifically to FOLR1-expressing cancer cells, VHH-P234 represents a promising innovation that addresses the therapeutic gap for patients with refractory or resistant forms of cancer, potentially enabling more efficient and safer interventions.