Next-Generation Trispecific Nanobody for Targeted Immunotherapy in Metastatic Prostate Cancer (FCGR3A & FOLH1)

VHH-P823 is a humanized trispecific nanobody engineered to selectively target two clinically validated antigens: Fc gamma receptor IIIa (FCGR3A) and folate hydrolase 1 (FOLH1). Currently in the Biological Testing development stage, VHH-P823 harnesses an innovative molecular design to engage both immune effector mechanisms and tumor specificity, representing a promising candidate for the treatment of metastatic prostate cancer. The dual targeting of FCGR3A and FOLH1 is designed to enhance anti-tumor efficacy by recruiting innate immune responses while ensuring selective cytotoxicity against prostate cancer cells, addressing critical unmet needs in advanced prostate malignancies.

Licensing Opportunity

VHH-P823 is currently available for out-licensing and strategic partnerships. We welcome inquiries from industry partners interested in advancing this innovative trispecific nanobody for metastatic prostate cancer into clinical development.

Development Phase

Modality

VHH-P823 is designed as a trispecific killer cell engager antibody that integrates an interleukin 15 crosslinker between an anti-CD16 single-domain antibody and a single-chain variable fragment directed against prostate-specific membrane antigen. This nanobody features a compact, single-domain antibody structure with notably small molecular size, granting it superior tissue penetration and stability compared to conventional antibodies. The unique trispecific configuration is optimized to bridge NK cells and tumor cells, facilitate immune synapse formation, and potentiate targeted immune activation in the tumor microenvironment. Such modality positions VHH-P823 as a differentiated, next-generation biologic for metastatic prostate cancer, leveraging advanced engineering to maximize clinical utility.

Target

FCGR3A and FOLH1 are highly relevant molecular targets in metastatic prostate cancer therapy. FCGR3A, primarily expressed on natural killer (NK) cells, is critical for mediating antibody-dependent cellular cytotoxicity (ADCC) and orchestrating innate immune activation. FOLH1, a membrane-bound enzyme with restricted expression in prostate tissue and significant upregulation in malignant prostate cells, serves as a hallmark for prostate cancer and metastatic lesions. By simultaneously engaging FCGR3A on immune effector cells and FOLH1 on tumor cells, VHH-P823 is strategically positioned for targeted cytotoxicity and immune potentiation in metastatic prostate cancer. Dual targeting of FCGR3A and FOLH1 maximizes tumor cell recognition while harnessing immune effector functions, providing a substantial asset for precision oncology applications.

Mechanism of Action

VHH-P823 employs a dual-engagement strategy by physically linking an anti-FCGR3A domain with a moiety targeting FOLH1, coupled via an interleukin 15 crosslinker. This molecular architecture brings NK cells, through FCGR3A binding, into close proximity with FOLH1-expressing prostate cancer cells, resulting in enhanced directed cytotoxicity and tumor cell elimination. The interleukin 15 element further stimulates NK cell proliferation and activity, intensifying immune responses in the tumor milieu. As a nanobody-based platform, VHH-P823 may be expanded to construct antibody–drug conjugates or multifunctional bispecifics, enabling broad applications across oncology and immunotherapy pipelines.

Metastatic Prostate Cancer

Metastatic prostate cancer is a leading cause of cancer-related morbidity and mortality among men worldwide, ranking as one of the most frequently diagnosed malignancies. Progression to metastatic disease is associated with poor prognosis and complex management challenges, as cancer cells spread beyond the prostate to bones, lymph nodes, and visceral organs. Standard treatment modalities include hormone therapy, chemotherapy, radiation, and targeted therapies. Despite advances, resistance to existing treatments and significant toxicity profiles limit clinical success, and many patients eventually progress to castration-resistant, metastatic disease. There remains a critical unmet need for innovative therapies that offer durable anti-tumor responses, improved safety, and precision targeting. VHH-P823, through trispecific immune engagement and heightened tumor specificity, holds promise as an advanced immunotherapeutic for addressing these urgent clinical gaps in metastatic prostate cancer management.