Dual Immune Checkpoint Bispecific Nanobody for Cancer Therapy Targeting CD274 and CD47
VHH-P352 is a bispecific, humanized nanobody-based antibody therapeutic that targets both CD274 molecule (CD274) and CD47 molecule (CD47). It is currently in the Biological Testing phase and is being developed as an innovative immunotherapy candidate for the treatment of cancer. By simultaneously addressing these two immunoregulatory molecules, VHH-P352 shows promise in enhancing anti-tumor immune responses. The program leverages the specificity and versatility of single domain nanobody technology, designed for applications across a broad cancer patient population.
| Candidate | VHH-P352 |
| Target | CD274 molecule (CD274) CD47 molecule (CD47) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P352 is available for out-licensing and collaborative development opportunities. We welcome partners interested in advancing this bispecific nanobody program toward clinical and commercial realization in oncology.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P352 |
Modality
VHH-P352 is a bispecific biologic constructed by fusing a monoclonal IgG1 anti-programmed death-ligand 1 antibody to a single domain anti-CD47 nanobody at the C-terminus of the light chain, utilizing a GGGGSGGGGS flexible linker. Expressed in human embryonic kidney cells, this structure incorporates the unique advantages of nanobodies, such as compact size, high solubility, and remarkable stability. These properties enhance tumor penetration and enable efficient targeting of heterogeneous cancer tissues. The modular format of VHH-P352 provides broader therapeutic potential over conventional monoclonal antibodies for cancer by enabling dual checkpoint blockade with optimized pharmacological properties and simplified manufacturing.
Target
CD274 and CD47 are pivotal immune checkpoint molecules implicated in tumor immune evasion. CD274, commonly expressed on tumor cells and myeloid cells, interacts with immune effector cells to inhibit anti-tumor responses. CD47 is a widely expressed transmembrane protein functioning as a “don’t eat me” signal, primarily on healthy and malignant hematopoietic, as well as solid tumor cells, inhibiting phagocytosis by macrophages. Both CD274 and CD47 are highly relevant targets in cancer therapy, as their upregulation is associated with poor clinical outcomes. VHH-P352 strategically targets CD274 and CD47 to overcome dual mechanisms of tumor immune escape, representing a promising approach for broadly enhancing cancer immunotherapy efficacy.
Mechanism of Action
VHH-P352 functions by concurrently blocking CD274 and CD47, both integral immune checkpoints in the tumor microenvironment. By inhibiting CD274, VHH-P352 restores T cell activity suppressed by the tumor. Simultaneously, antagonism of CD47 disrupts the “don’t eat me” signal, enabling macrophage-mediated phagocytosis of cancer cells. This dual action potentiates both innate and adaptive anti-tumor immune responses, which are often independently compromised in cancer. The nanobody-based platform also allows for the potential expansion into antibody-drug conjugates or modular bispecific antibodies targeting additional oncogenic pathways, establishing a versatile basis for future cancer immunotherapy innovations.
Cancer
Cancer encompasses a complex group of diseases characterized by uncontrolled cellular proliferation and invasion. Globally, cancer represents a leading cause of morbidity and mortality, affecting millions of individuals across diverse populations. The primary treatment strategies for cancer currently include surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. While these modalities have improved survival in many cancer types, challenges such as drug resistance, off-target toxicity, and tumor immune evasion persist. Despite advances in targeted therapies and immune checkpoint inhibitors, there remains a significant unmet clinical need for innovative treatments that address refractory disease and complex tumor microenvironments. VHH-P352, with its innovative dual-targeting approach to both CD274 and CD47, has the therapeutic potential to synergistically enhance anti-tumor immunity and overcome major mechanisms of resistance, offering new hope for patients with difficult-to-treat malignancies.