Innovative Bispecific Nanobody Targeting NT5E and CD274 for Cancer Immunotherapy
VHH-P551 is a humanized nanobody-based therapeutic currently in the Biological Testing stage, designed to simultaneously target 5'-nucleotidase ecto (NT5E) and CD274 molecule (CD274), also known as PD-L1. This bispecific antibody construct capitalizes on dual immune checkpoint modulation, presenting a promising approach for cancer therapy. By targeting both NT5E and CD274, VHH-P551 aims to disrupt critical pathways involved in tumor immune evasion, potentially enhancing antitumor immune responses. The novel design and precise specificity underscore its potential in advancing cancer treatment options and addressing unmet clinical needs in oncology.
| Candidate | VHH-P551 |
| Target | 5'-nucleotidase ecto (NT5E) CD274 molecule (CD274) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P551 is available for out-licensing and partnership opportunities. We welcome collaboration with industry partners to advance the clinical development and commercialization of this promising nanobody-based cancer immunotherapy.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P551 |
Modality
VHH-P551 is a tetravalent, symmetric bispecific antibody fusion construct that incorporates two antigen-binding fragments derived from IgG antibodies targeting CD73 and two heavy chain variable domains specifically recognizing programmed cell death protein 1 ligand (PD-L1). These are fused to an IgG1 Fc domain with engineered L234A and L235A mutations. As a nanobody-based modality, VHH-P551 represents a class of single-domain antibodies characterized by small size, increased stability, and enhanced tissue penetration. These structural features enable improved tumor infiltration and favorable pharmacokinetics, potentially leading to superior efficacy in cancer immunotherapy compared to conventional antibodies.
Target
NT5E and CD274 serve as critical molecular targets in oncology. NT5E is a cell surface enzyme involved in adenosine production and immunosuppression, while CD274 is a key immune checkpoint protein that inhibits T-cell activation. Both NT5E and CD274 are frequently overexpressed in various tumor types and within the tumor microenvironment, particularly on cancer cells and infiltrating immune cells. Targeting NT5E and CD274 interrupts immunosuppressive signaling pathways, restoring antitumor immunity. VHH-P551's dual specificity for NT5E and CD274 strategically positions it to counteract multiple mechanisms of immune escape, offering a distinctive advantage in the current immuno-oncology landscape and representing a valuable asset for cancer drug development.
Mechanism of Action
VHH-P551 exerts its therapeutic effects through simultaneous blockade of NT5E and CD274, acting as a dual immune checkpoint inhibitor. By binding to NT5E, the nanobody inhibits the enzymatic generation of adenosine, a metabolite that suppresses anti-tumor immune responses. Concurrently, targeting CD274 disrupts its interaction with PD-1 receptors on T cells, lifting inhibitory signaling and restoring immune cell activity against cancer cells. The bispecific architecture of VHH-P551 makes it a versatile platform, with the potential for further development into antibody-drug conjugates or multifunctional therapeutics, thereby expanding its applicability in immuno-oncology.
Cancer
Cancer represents a complex group of diseases characterized by uncontrolled cell proliferation and the ability of malignant cells to invade surrounding tissues and metastasize to distant organs. It remains a major global health burden, with incidence rates continuing to rise due to various genetic and environmental risk factors. Current mainstays of cancer treatment include surgery, chemotherapy, radiation therapy, and molecularly targeted therapies, as well as immunotherapies such as immune checkpoint inhibitors. However, many patients experience limited responses or develop resistance to existing treatments. There is a significant unmet clinical need for novel therapies that can overcome tumor-induced immunosuppression and effectively eradicate malignancies. By targeting two key immunomodulatory proteins, VHH-P551 offers the potential to address these challenges and provide an innovative treatment option for patients with cancer.