Bispecific Nanobody Targeting CD3 Complex and TNFRSF13C for Innovative Lymphoma Treatment
VHH-P265 is a humanized bispecific nanobody designed to precisely target both the CD3 Complex (T Cell Receptor Complex) and TNF receptor superfamily member 13C (TNFRSF13C). Currently in the Biological Testing stage, VHH-P265 harnesses the therapeutic potential of engaging T cells and modulating B cell signaling, aiming to provide a novel modality for lymphoma treatment. By leveraging these two crucial immunological targets, the program seeks to address unmet needs in the management of lymphoma and lays the foundation for next-generation immunotherapeutics.
| Candidate | VHH-P265 |
| Target | CD3 Complex (T Cell Receptor Complex) TNF receptor superfamily member 13C (TNFRSF13C) |
| Modality | humanized bispecific VHH |
| Indication | Lymphoma |
Licensing Opportunity
VHH-P265 is available for out-licensing and strategic collaborations. We welcome inquiries from partners interested in advancing innovative immunotherapies for the treatment of lymphoma.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P265 |
Modality
VHH-P265 utilizes a unique bispecific antibody fusion construct, consisting of two polypeptide chains. The first chain integrates a single-domain antibody against the human B-cell activating factor receptor, fused to an anti-CD3 fragment and a human IgG4 Fc domain. The second chain comprises an anti-BAFF-R VHH linked to a human IgG4 Fc domain, engineered with stabilizing mutations. Expressed in CHO-S cells, the nanobody features a compact, single-domain structure that confers enhanced tissue penetration and stability. This molecular architecture offers potential advantages for lymphoma therapy, including improved tumor targeting and manufacturability.
Target
CD3 Complex is a critical surface protein complex expressed on all T cells and is essential for T cell activation and immune signaling. TNFRSF13C is predominantly found on mature B cells, functioning as a receptor involved in B cell survival and proliferation. Both CD3 Complex and TNFRSF13C are validated immuno-oncology targets, implicated in the dysregulation observed in various lymphomas. Targeting CD3 Complex empowers T cell-mediated cytotoxicity against lymphoma cells, while modulating TNFRSF13C disrupts malignant B cell growth. VHH-P265's dual targeting of CD3 Complex and TNFRSF13C represents a strategic asset for precision lymphoma immunotherapy.
Mechanism of Action
VHH-P265 mediates its therapeutic effect through simultaneous engagement of CD3 Complex on T cells and TNFRSF13C on B cells or lymphoma cells. By bringing T cells into close proximity with malignant B cells, the molecule promotes T cell activation and directed cytotoxicity. Signal transduction modulation at the tumor site further amplifies anti-lymphoma activity. This approach capitalizes on the potent T-cell engager mechanism, with the nanobody-based platform supporting further expansion into bispecific and multispecific antibody formats, as well as other modular applications such as antibody-drug conjugates.
Lymphoma
Lymphoma encompasses a diverse group of hematological malignancies originating from lymphocytes, including both Hodgkin and non-Hodgkin subtypes. It represents one of the most common cancers globally, with rising incidence in certain regions. Standard treatments include chemotherapy, radiotherapy, and targeted agents; however, resistance, relapse, and adverse effects remain persistent challenges. Immunotherapies such as T cell engagers have shown promise, but many patients still lack effective, durable solutions. The dual targeting of CD3 Complex and TNFRSF13C by VHH-P265 offers a differentiated immunotherapy strategy, addressing both malignant B cell survival and facilitating immune-mediated tumor clearance.