First-in-Class Bispecific Nanobody Targeting FCGR3A and MUC16 for Precision Cancer Therapy

VHH-P593 is an innovative, humanized nanobody designed to selectively bind Fc gamma receptor IIIa (FCGR3A) and mucin 16, cell surface associated (MUC16). Currently in the Biological Testing stage, VHH-P593 harnesses the specificity and modularity of single-domain antibodies to enable targeted cancer therapy. By engaging both key surface proteins implicated in tumor progression and immune modulation, VHH-P593 demonstrates promising potential to advance treatment strategies for cancer. The program leverages advanced antibody engineering to optimize tumor cell targeting and facilitate immune cell recruitment, positioning VHH-P593 as a valuable asset in the growing field of immuno-oncology.

Licensing Opportunity

VHH-P593 is available for out-licensing and collaborative development. We welcome partnerships with industry leaders and innovative organizations seeking to expand their oncology pipelines with next-generation bispecific nanobody therapeutics.

Development Phase

Modality

VHH-P593 is a bispecific antibody fusion construct featuring two alpaca-derived single-domain antibodies: one against CD16 and another against the anti-cancer antigen 125 (CA125/MUC16). These are joined via a flexible (G4S)4 linker and fused to a human IgG1 Fc domain, enhancing effector functions and in vivo stability. The nanobody’s small molecular size enables superior tumor penetration compared to traditional antibodies, while its robust structure confers exceptional stability. Expression in human HEK293 cells makes it suitable for scalable manufacturing. For cancer treatment, this modality supports dual targeting, improved immune cell engagement, and optimal pharmacokinetic properties, addressing critical challenges in solid tumor therapy.

Target

FCGR3A is a low-affinity receptor for the Fc portion of immunoglobulin G, predominantly expressed on the surface of natural killer (NK) cells and certain myeloid populations. FCGR3A mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in immunotherapy. MUC16 is a high molecular weight glycoprotein overexpressed on the surface of various cancer cells, notably ovarian tumors, and is associated with tumor progression, metastasis, and immune evasion. The co-expression of FCGR3A on immune effector cells and MUC16 on tumor cells makes them strategic, complementary targets for bispecific therapeutics. VHH-P593’s dual engagement of FCGR3A and MUC16 facilitates selective recruitment and activation of immune effector cells directly at the tumor site, maximizing anti-tumor responses. Strategically, this dual targeting enhances specificity, reduces off-target effects, and underscores VHH-P593’s unique value in the cancer immunotherapy landscape.

Mechanism of Action

VHH-P593 exerts its therapeutic effects by simultaneously binding FCGR3A on NK cells and MUC16 on cancer cells. This dual targeting enables the nanobody to function as an NK-cell engager, physically bridging immune effector cells with malignant targets. Upon engagement, FCGR3A triggers NK cell activation, leading to antibody-dependent cellular cytotoxicity against MUC16-expressing tumor cells. The bispecific design may also modulate downstream signal transduction pathways in both immune and cancer cells, enhancing anti-tumor activity. The nanobody format of VHH-P593 supports future adaptation into additional formats, such as antibody-drug conjugates or multi-specific antibodies, expanding its applicability across different oncological indications and boosting the platform’s therapeutic versatility.

Cancer

Cancer is a complex group of diseases characterized by uncontrolled cell growth and the potential for metastasis to distant organs. It remains one of the world’s leading causes of morbidity and mortality, with new diagnoses and deaths projected to rise as populations age. Standard therapies include surgical intervention, chemotherapy, radiation therapy, targeted agents, and immunotherapies. Despite these advances, many patients face limited treatment efficacy, drug resistance, significant side effects, or relapse, highlighting substantial unmet medical needs. Current immunotherapies have shown promise, yet only benefit select patient subsets, and many tumors remain refractory due to immune evasion strategies such as altered antigen expression or suppression of cytotoxic lymphocytes. The VHH-P593 program offers a novel therapeutic approach by leveraging bispecific nanobody technology to enhance tumor cell recognition and immune engagement. By specifically targeting both MUC16 on tumor cells and FCGR3A on immune effectors, VHH-P593 may help overcome key resistance mechanisms and improve therapeutic outcomes for diverse cancer subtypes.