Next-Generation Trifunctional Nanobody Targeting CD24 and NCR3 for Innovative Cancer Therapy
VHH-P547 is a humanized nanobody-based trifunctional antibody currently in the Biological Testing stage, designed for therapeutic intervention in cancer. This novel construct specifically targets both CD24 molecule (CD24) and natural cytotoxicity triggering receptor 3 (NCR3), integrating advanced antibody engineering to maximize antitumor efficacy. By leveraging unique epitope recognition on CD24 and NCR3, VHH-P547 aims to enhance immune-mediated elimination of cancer cells. Its development signifies a new approach in the use of single-domain antibody platforms, aiming to address unmet needs in oncology and potentially transform cancer treatment paradigms.
| Candidate | VHH-P547 |
| Target | CD24 molecule (CD24) natural cytotoxicity triggering receptor 3 (NCR3) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P547 is actively available for out-licensing opportunities. We invite partners interested in innovative cancer immunotherapies to collaborate in advancing this promising nanobody-based program toward clinical and commercial success.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P547 |
Modality
VHH-P547 is engineered as a trifunctional antibody that combines an anti-CD24 monoclonal antibody with an N-terminal fusion to a single-domain nanobody targeting natural killer protein 30. Additionally, interleukin-15 and IL-15 receptor alpha sushi variant sequences are inserted between the CH1 and CH2 domains of the anti-CD24 backbone. Produced using Escherichia coli DH5alpha cells, the nanobody component offers a compact single-domain structure, imparting superior tissue penetration and increased stability compared to conventional IgG antibodies. This architecture is particularly advantageous for cancer therapy, potentially facilitating deeper tumor infiltration, greater solubility, and improved functional activity in the tumor microenvironment.
Target
CD24 is a glycosylphosphatidylinositol-anchored membrane protein implicated in cellular adhesion, immune evasion, and tumor progression, commonly expressed on various malignancies as well as on hematopoietic and tumor cells. NCR3 is an activating receptor found predominantly on natural killer (NK) cells, where it plays a critical role in innate immune surveillance by mediating cytotoxic responses against tumor targets. Both CD24 and NCR3 are recognized as strategic cancer therapy targets due to their involvement in immune regulation and tumor immune escape. The dual targeting of CD24 and NCR3 by VHH-P547 is designed to disrupt tumor cell defenses and sensitize them to NK cell-mediated killing, establishing a differentiated and strategic profile within the oncology therapeutic landscape.
Mechanism of Action
VHH-P547 operates through coordinated targeting of CD24 and NCR3. By binding to CD24 on tumor cells, the antibody disrupts signal transduction pathways implicated in immune evasion and cell proliferation. Simultaneous engagement of NCR3 on natural killer cells enhances their cytolytic activity, encouraging direct elimination of malignant cells. The engineered inclusion of interleukin-15 and IL-15 receptor segments may further potentiate NK cell activation. This mechanism promotes effective antitumor immunity by bridging innate and adaptive responses. The nanobody platform of VHH-P547 also provides a foundation for generating advanced therapeutics, such as antibody-drug conjugates or bispecific constructs, expanding its applicability within oncology.
Cancer
Cancer remains a leading cause of morbidity and mortality worldwide, encompassing a heterogeneous group of diseases characterized by uncontrolled cell growth and potential for metastatic spread. Current treatment modalities include surgery, chemotherapy, radiotherapy, immunotherapy, and targeted biologics. Despite significant advances, conventional therapies are often associated with limited efficacy, severe side effects, and the emergence of resistance. There exists a persistent unmet medical need for novel agents capable of overcoming tumor immune evasion and providing durable responses. VHH-P547 is poised to address these challenges by exploiting dual-immune pathway targeting, potentially enhancing antitumor activity and achieving improved clinical outcomes for patients with diverse malignancies.