Innovative Bispecific Nanobody Engager Targeting FCGR3A and PTPRC for Cancer Immunotherapy

VHH-P385 is a fully humanized bispecific nanobody designed to target Fc gamma receptor IIIa (FCGR3A) and protein tyrosine phosphatase receptor type C (PTPRC). Currently in the Biological Testing stage, VHH-P385 leverages a dual-targeting approach to enhance the anti-tumor immune response, offering a novel mechanism for cancer therapy. By engaging both human natural killer cell receptors and cell-surface antigens on hematopoietic cells, this advanced molecule holds significant promise for addressing a broad range of cancer indications, supporting the pursuit of more effective and selective immunotherapeutic strategies.

Licensing Opportunity

VHH-P385 is available for out-licensing and strategic partnership. We invite inquiries from biopharmaceutical companies seeking novel immuno-oncology assets and collaborative development opportunities.

Development Phase

Modality

VHH-P385 employs a bispecific nanobody-based modality, consisting of a codon-optimized single-chain variable fragment targeting CD45 (PTPRC) fused to a single-domain antibody that recognizes human CD16 (FCGR3A). This nanobody architecture provides intrinsic advantages, including a small molecular size and robust tissue penetration, which facilitate efficient immune cell engagement within tumor microenvironments. High solubility and thermal stability further enhance its manufacturability and pharmacokinetic profile. As a next-generation NK-cell engager, VHH-P385 is designed for precise redirection of cytotoxic immune cells against malignancies, enabling potent anti-tumor effects while minimizing off-target toxicity in cancer therapy.

Target

FCGR3A and PTPRC are pivotal immunotherapeutic targets for cancer. FCGR3A, a low-affinity receptor for the Fc portion of immunoglobulin G, is prominently expressed on natural killer (NK) cells and is crucial for initiating antibody-dependent cell-mediated cytotoxicity. PTPRC is a transmembrane protein tyrosine phosphatase expressed broadly on all nucleated hematopoietic cells, playing a fundamental role in immune signaling and cell differentiation. Aberrant regulation of FCGR3A or PTPRC is frequently implicated in tumor immune evasion. Targeting both FCGR3A and PTPRC enables dual modulation: VHH-P385 can simultaneously recruit and activate NK cells (via FCGR3A) while recognizing pathogenic hematopoietic cell populations (via PTPRC). This strategic bispecific action uniquely positions VHH-P385 to synergize anti-cancer immunity and expands its potential across hematologic and solid tumor settings.

Mechanism of Action

VHH-P385 exerts its activity through a dual mechanism, engaging both FCGR3A on NK cells and PTPRC on target cancer cells. By binding FCGR3A, VHH-P385 anchors and activates NK cells, promoting the formation of an immunological synapse for targeted cytotoxicity. Concurrently, the antibody directs these activated NK cells towards malignant cells expressing PTPRC, enhancing immune specificity and minimizing collateral damage to healthy tissues. This nanobody-based platform inherently facilitates modular engineering, allowing for expansion into antibody-drug conjugates or multivalent bispecifics for tailored oncology applications. The action of VHH-P385 represents a new generation of targeted NK-cell engagers, combining precision, adaptability, and enhanced tumor clearance.

Cancer

Cancer remains one of the leading health challenges worldwide, responsible for high morbidity and mortality across populations. The disease encompasses diverse solid tumors and hematological malignancies, characterized by unregulated cellular proliferation and the ability to evade immune surveillance. Current treatment modalities include surgery, chemotherapy, radiotherapy, immunotherapy, and targeted biologicals. While recent advancements in immunotherapy have offered improved outcomes for subsets of patients, significant limitations persist, including resistance, non-specific toxicity, and limited efficacy in heterogeneous tumor environments. The need for more selective, potent, and safer therapies remains unmet in many cancer types. VHH-P385, as a bispecific nanobody NK-cell engager targeting FCGR3A and PTPRC, represents a promising innovation, with the potential to overcome resistance and enhance anti-tumor immune responses through precision cellular engagement.