Innovative Nanobody-Based Trispecific Engager Targeting CD276 and FCGR3A for Ovary Cancer Therapy
VHH-P526 is a novel humanized nanobody therapeutic candidate that targets the CD276 molecule (CD276) and Fc gamma receptor IIIa (FCGR3A), developed for the potential treatment of ovary cancer. Currently in the biological testing phase, VHH-P526 features a bispecific design, aiming to leverage immune cell redirection for enhanced antitumor activity. By combining specificities for CD276 and FCGR3A, two clinically relevant targets implicated in ovarian malignancy, this investigational modality exemplifies the next-generation approach in onco-immunotherapy. Its distinctive design and biological rationale position VHH-P526 as a promising solution for unmet medical needs in ovarian cancer.
| Candidate | VHH-P526 |
| Target | CD276 molecule (CD276) Fc gamma receptor IIIa (FCGR3A) |
| Modality | humanized bispecific VHH |
| Indication | Ovary Cancer |
Licensing Opportunity
VHH-P526 is currently available for out-licensing and collaborative partnerships. We welcome inquiries from biopharmaceutical companies and research organizations interested in advancing innovative therapeutics for ovary cancer.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P526 |
Modality
VHH-P526 is a second-generation trispecific killer cell engager constructed from a humanized camelid-derived single-domain antibody, fused sequentially to human interleukin-15 and a single-chain variable fragment. The nanobody architecture (single-domain antibody) provides enhanced tissue penetrability, stability, and reduced immunogenicity due to its small molecular size and unique structure. These characteristics enable efficient engagement of immune effector functions while facilitating tumor infiltration, which is particularly beneficial in solid tumors like ovary cancer. Expression in Escherichia coli BL21 further enables robust and scalable manufacturing, adding to commercial viability for broad clinical application.
Target
CD276 and FCGR3A are protein molecules integral to tumor immune evasion and immune cell activation, respectively. CD276 belongs to the B7 family of immune regulatory proteins and is frequently overexpressed on tumor cells, including ovary cancer, where it contributes to immune escape. FCGR3A is an activating receptor expressed predominantly on natural killer (NK) cells and certain subsets of macrophages, mediating antibody-dependent cellular cytotoxicity. The dual targeting of CD276 and FCGR3A addresses both tumor cell recognition and immune effector activation. By engaging CD276 and FCGR3A, VHH-P526 offers a strategic advantage in selectively directing cytotoxic immune activity towards tumor sites, underlining its clinical development value in ovary cancer treatment paradigms.
Mechanism of Action
VHH-P526 operates as a trispecific NK-cell engager by simultaneously binding CD276 on ovarian tumor cells and FCGR3A on immune effector cells. The engineered fusion with interleukin-15 augments NK-cell activation and proliferation in the tumor microenvironment. Through this dual engagement of CD276 and FCGR3A, the molecule facilitates immune synapse formation, enhancing tumor cell recognition and targeted cytotoxicity. The nanobody platform offers modularity for potential expansion into formats such as bispecifics, multivalent constructs, or antibody–drug conjugates. The collective mechanism positions VHH-P526 as a versatile agent with broad applications in immune-based cancer therapy.
Ovary Cancer
Ovary cancer, a significant cause of cancer-related morbidity and mortality among women worldwide, is often diagnosed at an advanced stage due to nonspecific early symptoms. Epidemiological data highlight its substantial global burden. Standard of care includes surgical resection, cytotoxic chemotherapy, and, in select cases, targeted or immunotherapeutic approaches. Despite recent advances, challenges persist, such as chemoresistance, disease recurrence, and adverse side effects, underscoring persistent unmet medical needs. Novel agents that harness the immune system or specifically address tumor immune evasion mechanisms represent a promising frontier. VHH-P526, with its dual targeting of tumor and immune effector cells and enhanced tissue penetration, has the therapeutic potential to improve outcomes for patients with ovary cancer, particularly those refractory to traditional modalities.