Next-Generation Bispecific Nanobody Targeting FCGR3A and TNFRSF17 for Cancer Immunotherapy

VHH-P571 is a humanized nanobody-based bispecific antibody candidate designed to simultaneously target Fc gamma receptor IIIa (FCGR3A) and TNF receptor superfamily member 17 (TNFRSF17), two clinically relevant molecules in cancer immunotherapy. Currently in the Biological Testing development stage, VHH-P571 represents a novel approach with high translational potential in addressing the therapeutic challenges present in cancer. By leveraging its dual-targeting capability, VHH-P571 aims to harness both innate and adaptive immune responses, potentially providing improved efficacy over traditional monoclonal antibodies. This innovative candidate is being explored for its ability to mediate potent anti-tumor effects through precise immune modulation.

Licensing Opportunity

VHH-P571 is now available for out-licensing and strategic collaborations. We welcome inquiries from partners seeking innovative bispecific nanobody assets in the field of cancer immunotherapy to accelerate development and commercialization.

Development Phase

Modality

VHH-P571 is a bispecific antibody constructed from two specialized chains: the first chain comprises an anti-CD16A single-domain antibody (nanobody) fused to an engineered IgG1 Fc region with knob mutations, and the second chain features an anti-B cell maturation antigen fragment fused to an IgG1 Fc region with a complementary hole mutation. Engineered using knob-into-hole technology and produced in HEK293F cells, this format ensures correct pairing and structural integrity. The nanobody modality offers significant advantages for cancer therapy, such as reduced molecular size promoting deeper tumor penetration and increased stability in challenging physiological environments. The fusion to human IgG1 Fc further provides extended half-life and effector function, crucial for effective tumor cell targeting and immune engagement.

Target

FCGR3A and TNFRSF17 are two pivotal targets in the landscape of cancer immunotherapy. FCGR3A is a low-affinity Fc receptor, highly expressed on natural killer (NK) cells and certain other immune cells, where it mediates antibody-dependent cellular cytotoxicity. TNFRSF17, primarily found on malignant and normal plasma cells and some mature B cell populations, plays a role in cell survival and proliferation. Both FCGR3A and TNFRSF17 are involved in tumor immunology, making them attractive targets for intervention. FCGR3A enables recruitment and activation of immune effector cells at the tumor site, while TNFRSF17 is frequently overexpressed in hematologic malignancies and supports cancer cell viability. By simultaneously targeting FCGR3A and TNFRSF17, VHH-P571 enables concerted innate and adaptive immune responses, underpinning its strategic value in cancer immunotherapy.

Mechanism of Action

VHH-P571 mediates its anti-cancer activity through a dual-engagement strategy. The anti-FCGR3A chain interacts selectively with NK cells, leveraging their cytotoxic potential through engagement of the Fc receptor, while the TNFRSF17-specific chain binds to B cell lineage malignant cells. By bridging FCGR3A on immune effector cells and TNFRSF17 on tumor cells, VHH-P571 instigates potent NK cell-mediated cytotoxicity against cancer targets. This bispecific modality not only directly eliminates malignant cells but also modulates relevant signal transduction pathways involved in tumor survival and immune escape. The nanobody platform is highly versatile and can be further developed into advanced constructs such as antibody-drug conjugates or multispecific engagers, expanding the therapeutic landscape for diverse oncology indications.

Cancer

Cancer represents a complex group of diseases characterized by the uncontrolled growth and spread of abnormal cells, remaining a leading cause of morbidity and mortality worldwide. Despite significant advancements in surgery, radiation, chemotherapy, and targeted therapies, cancer continues to pose major global health challenges due to its heterogeneity and capacity for immune evasion. Current therapies, including immunotherapy and cellular therapies, have improved outcomes for certain patient groups, yet a large proportion of patients experience relapse or fail to respond, underscoring critical unmet needs. The limitations include drug resistance, toxicity, and a lack of effective options for specific tumor types. Bispecific antibodies like VHH-P571 have the potential to address these shortcomings by targeting tumor cells and activating immune effectors with high specificity, offering a promising new approach to enhance anti-tumor response and improve patient prognosis in various cancer settings.