Next-Generation Nanobody Immunotherapy Targeting CD3E and FOLH1 for Prostate Cancer

VHH-P782 is an innovative humanized nanobody-based biologic, currently in the Biological Testing stage of development, designed for the treatment of prostate cancer. This trispecific molecule precisely targets the CD3 epsilon subunit of the T-cell receptor complex (CD3E) and folate hydrolase 1 (FOLH1), both critical in tumor immunology and prostate cancer pathogenesis. Through a unique molecular architecture, VHH-P782 is positioned as a promising candidate capable of harnessing immune redirection mechanisms to enhance therapeutic efficacy in prostate cancer.

Licensing Opportunity

VHH-P782 is available for out-licensing or strategic collaboration. We welcome partners interested in advancing innovative nanobody-based immunotherapies for prostate cancer. Contact us for more information on partnership opportunities.

Development Phase

Modality

VHH-P782 utilizes a trispecific format built from single-domain antibodies (nanobodies), providing high specificity and low molecular weight. The molecule incorporates a nanobody targeting human prostate specific membrane antigen (PSMA/FOLH1), a domain for human serum albumin to enhance serum half-life, and a single-chain V-domain fragment against CD3E, all linked by glycine-serine-rich linkers. This modular design, expressed in Expi293 cells, offers favorable tissue penetration and stability, potentially overcoming traditional antibody limitations in solid tumor therapy. The compact structure and high stability of nanobodies enable effective delivery to prostate tumor sites, supporting robust T-cell engagement and immune activation while minimizing off-target effects.

Target

CD3E and FOLH1 are pivotal targets in the landscape of prostate cancer immunotherapy. CD3E, a component of the T-cell receptor complex, plays a vital role in T-cell activation and immune modulation. Its selective engagement enables precise recruitment of T-cells to tumor sites. FOLH1, an established prostate cancer marker, is overexpressed on malignant prostate cells and involved in tumor progression and aggressiveness. Targeting FOLH1 ensures tumor specificity, while CD3E engagement triggers potent immune responses. The dual targeting by VHH-P782 of both CD3E and FOLH1 provides a strategic advantage, potentially improving selectivity and therapeutic index in prostate cancer. The simultaneous interaction with CD3E and FOLH1 positions VHH-P782 as a next-generation immunotherapeutic asset for addressing resistance and heterogeneity in prostate cancer.

Mechanism of Action

VHH-P782 exerts its anti-tumor activity through selective binding to FOLH1 on prostate cancer cells and CD3E on T cells. This interaction re-directs and activates T lymphocytes towards tumor cells expressing FOLH1, resulting in targeted cell-mediated cytotoxicity. By bridging T cells with malignant prostate cells, VHH-P782 initiates immune synapse formation and signal transduction via CD3E, enhancing T cell activation and tumor cell lysis. This platform leverages the versatility of nanobodies, which can be further engineered for derivatives such as bispecifics or antibody-drug conjugates, offering expanded therapeutic applications and adaptability to different cancer targets.

Prostate Cancer

Prostate cancer is one of the most prevalent malignancies in men globally, with incidence rates steadily rising, particularly in aging populations. Standard approaches include surgery, radiation therapy, hormone therapy, chemotherapy, and targeted biologics, each offering varying degrees of disease control. Challenges remain, such as treatment resistance, metastatic progression, and toxicity from conventional therapies. Despite advances, there is a substantial need for novel strategies that deliver greater specificity and durable responses. The emergence of immunotherapies targeting tumor-associated antigens, such as FOLH1, represents a significant step forward. VHH-P782 addresses these unmet needs by combining the specificity for prostate tumor markers with immune effector cell activation, offering promising potential for improved outcomes in patients with limited therapeutic options.