A Next-Generation Bispecific Nanobody Targeting CD276 and CD47 for Cancer Immunotherapy
VHH-P427 is a humanized nanobody-based bispecific antibody fusion construct currently in the Biological Testing stage, with promising therapeutic potential for the treatment of cancer. This innovative molecule integrates an antigen-binding domain targeting CD276 molecule (CD276) and a single domain antibody directed against CD47 molecule (CD47), fused to a human IgG1 Fc domain. By simultaneously engaging both CD276 molecule (CD276) and CD47 molecule (CD47), VHH-P427 is designed to modulate tumor immune evasion and enhance anti-tumor activity. Its advanced engineering and dual-target approach position it as a novel candidate in the evolving landscape of cancer immunotherapy.
| Candidate | VHH-P427 |
| Target | CD276 molecule (CD276) CD47 molecule (CD47) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P427 is available for out-licensing and collaboration. We invite partners interested in advancing next-generation bispecific nanobody therapeutics in oncology to connect for detailed discussions and shared development opportunities.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P427 |
Modality
VHH-P427 is designed as a bispecific fusion antibody that combines two distinct binding domains: a conventional antigen-binding domain for CD276 and a nanobody (single-domain antibody) for CD47, linked via a human IgG1 Fc region. The nanobody format offers several structural advantages, including smaller molecular size, high stability, and exceptional tissue penetration—especially valuable in targeting solid tumors associated with cancer. The dual-targeting design can engage both immune checkpoint proteins simultaneously, allowing for broader immune modulation. The Fc fusion enhances half-life and effector function, making VHH-P427 a highly versatile and potent modality for cancer therapy.
Target
CD276 and CD47 are pivotal immune checkpoint molecules implicated in tumor immune evasion. CD276, a member of the B7 family, is often overexpressed on tumor cells and tumor vasculature but limited on normal tissues, supporting its role as a selective target in cancer. CD47 is widely expressed in many cancers, acting as a 'don't eat me' signal to macrophages and thereby hindering innate immune clearance. Together, CD276 and CD47 facilitate the survival and progression of malignant cells. By co-targeting CD276 and CD47, VHH-P427 aims to disrupt two distinct immune escape mechanisms, maximizing anti-tumor immunity while sparing normal tissues. The dual blockade offers strategic value for developing more effective cancer immunotherapies targeting CD276 and CD47.
Mechanism of Action
VHH-P427 acts by simultaneously binding CD276 and CD47 with high specificity. CD276 blockade leads to enhanced T cell-mediated immune responses against tumor cells, while inhibition of CD47 alleviates its suppression of macrophage-mediated phagocytosis, promoting innate immune clearance of cancer cells. This dual immune checkpoint inhibition amplifies the anti-tumor environment, overcoming major resistance mechanisms that enable tumor persistence. The nanobody platform enables the generation of innovative modalities such as antibody-drug conjugates and further multispecific constructs, expanding potential therapeutic applications for oncology. VHH-P427 thus provides a robust foundation for next-generation immuno-oncology treatments targeting CD276 and CD47.
Cancer
Cancer remains one of the leading causes of morbidity and mortality worldwide, affecting millions of people each year. Cancer comprises a broad group of diseases characterized by uncontrolled cell proliferation and potential metastasis to distant organs. The mainstay treatment modalities include surgery, radiotherapy, chemotherapy, targeted agents, and immunotherapy. However, current therapies are often limited by drug resistance, insufficient tumor selectivity, and significant side effects. There is a substantial unmet need for therapies that overcome immune suppression in the tumor microenvironment and enhance anti-tumor responses with improved safety. VHH-P427, by dually targeting CD276 and CD47 immune checkpoint pathways, addresses two critical aspects of tumor immune evasion and may offer superior efficacy in patients resistant or refractory to standard treatments. Its innovative mechanism holds considerable promise for improving cancer outcomes and expanding the reach of immunotherapy.