Innovative Bispecific Nanobody Targeting CD274 and CD276 for Melanoma Immunotherapy
VHH-P832 is a humanized nanobody-based bispecific antibody designed to target both CD274 molecule (CD274) and CD276 molecule (CD276). Currently in the Biological Testing stage of development, VHH-P832 demonstrates strong potential for the treatment of melanoma. This advanced construct utilizes the selectivity and stability of nanobody engineering, incorporating specific recognition of CD274 molecule (CD274) and CD276 molecule (CD276) to address immune evasion mechanisms in tumor microenvironments. Its development represents a promising addition to novel immunotherapeutic strategies in oncology, particularly for challenging indications such as melanoma.
| Candidate | VHH-P832 |
| Target | CD274 molecule (CD274) CD276 molecule (CD276) |
| Modality | humanized bispecific VHH |
| Indication | Melanoma |
Licensing Opportunity
VHH-P832 is available for partnering and out-licensing opportunities. We welcome collaboration discussions with industry and academic partners interested in advancing innovative therapies for melanoma.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P832 |
Modality
VHH-P832 is a tetravalent bispecific antibody, built by fusing a humanized IgG1 monoclonal antibody specific for CD274 with a humanized nanobody that recognizes CD276, using a flexible linker at the Fc C-terminal. Expression in human embryonic kidney cells ensures proper folding and post-translational modifications. The nanobody component provides a single-domain structure, offering compact size, high tissue penetration, and robust stability compared to conventional antibodies. This unique architecture enhances its ability to infiltrate tumor tissue in melanoma, improving target accessibility and therapeutic durability, and supports multifaceted immune checkpoint blockade within the tumor microenvironment.
Target
CD274 and CD276 are immune checkpoint molecules of the B7 family, with CD274 mediating inhibition of T cell activation, while CD276 is implicated in immune modulation in cancer. Both CD274 and CD276 are frequently expressed on tumor cells and tumor-associated stroma, particularly in melanoma. The overexpression of CD274 on melanoma cells enables evasion of immune surveillance, while CD276 is involved in promoting tumor growth and suppressing immune response. Dual targeting of CD274 and CD276 by VHH-P832 offers a strategic advantage by simultaneously blocking two non-redundant pathways of immune regulation in melanoma. By focusing on CD274 and CD276, VHH-P832 aims to enhance anti-tumor immunity and position itself as a next-generation immuno-oncology asset.
Mechanism of Action
VHH-P832 exerts its therapeutic effects by simultaneously engaging CD274 and CD276, two critical immune checkpoint molecules upregulated in the tumor microenvironment of melanoma. By binding to CD274, VHH-P832 prevents this inhibitor from interacting with its cognate receptor, thereby reinvigorating T cell activity. Concurrent targeting of CD276 disrupts additional immune suppressive signals and may augment anti-tumor responses. The bispecific format of VHH-P832 enables dual immune checkpoint blockade, potentiating cytotoxic lymphocyte function. Furthermore, the modular nanobody architecture allows for future expansion into bispecific, trispecific, or payload-conjugated formats like antibody-drug conjugates, broadening applications in immunotherapy.
Melanoma
Melanoma is a highly aggressive form of skin cancer originating from melanocytes, characterized by rapid progression and a tendency to metastasize. Globally, it presents an increasing health burden, with incidence rising in regions with predominantly fair-skinned populations. The primary approaches to melanoma management include surgical resection for localized disease, followed by systemic therapies such as chemotherapy, immune checkpoint inhibitors, and molecularly targeted agents for advanced cases. Despite advances in immunotherapy, a proportion of patients develop resistance or experience relapse, highlighting the need for novel treatment modalities. Tumor immune evasion, mediated in part by overexpression of immune checkpoint proteins like CD274 and CD276, remains a key obstacle. VHH-P832, with its dual blockade of these molecules, offers an innovative therapeutic avenue to potentially overcome resistance mechanisms and improve outcomes for patients with melanoma.