Next-Generation Bispecific Nanobody Targeting CD274 and PDCD1LG2 for Lung Cancer Immunotherapy
VHH-P817 is a fully humanized nanobody construct designed to target CD274 molecule (CD274) and programmed cell death 1 ligand 2 (PDCD1LG2), currently advancing through the biological testing stage. By engaging these key immune checkpoint regulators, VHH-P817 shows significant promise for the treatment of lung cancer. This innovative bispecific antibody format offers a novel approach to overcome tumor immune evasion, reinforcing anti-tumor immune responses in the tumor microenvironment. The modular architecture and dual-targeting strategy strongly position VHH-P817 as a next-generation immunotherapeutic candidate for lung cancer and potentially other malignancies where immune checkpoint pathways are dysregulated.
| Candidate | VHH-P817 |
| Target | CD274 molecule (CD274) programmed cell death 1 ligand 2 (PDCD1LG2) |
| Modality | humanized bispecific VHH |
| Indication | Lung Cancer |
Licensing Opportunity
VHH-P817 is now open for out-licensing and collaborative development opportunities. We invite partners interested in advancing next-generation nanobody immunotherapies in oncology to engage in discussions for potential collaboration.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P817 |
Modality
VHH-P817 is designed as a radiolabeled, N-Bromosuccinimide-conjugated bispecific nanobody construct, featuring two anti-CD274 and two anti-PDCD1LG2 nanobody domains. By leveraging single-domain (VHH) antibody technology, the molecule retains high specificity and binding affinity in a compact format. The small molecular size of nanobodies confers rapid tissue penetration and superior tumoral accumulation, which is particularly advantageous for lung cancer with heterogeneous and dense stroma. Radiolabeling with Iodine-124 also enables real-time imaging and pharmacodynamic monitoring. VHH constructs deliver enhanced stability and manufacturability relative to conventional antibodies, supporting their potential as both therapeutic and diagnostic agents in solid tumors.
Target
CD274 and PDCD1LG2 are type I transmembrane proteins that function as immune checkpoint molecules, playing critical roles in modulating T cell activity within the tumor microenvironment. Both CD274 and PDCD1LG2 are primarily expressed on tumor cells, antigen-presenting cells, and some stromal cells. In lung cancer, overexpression of CD274 and PDCD1LG2 contributes to immune suppression and tumor progression by inhibiting T cell-mediated cytotoxicity. Therapeutically targeting CD274 and PDCD1LG2 disrupts these immunosuppressive mechanisms, promoting anti-tumor immunity. VHH-P817, by confronting CD274 and PDCD1LG2 simultaneously, offers strategic advantages for tumor control in lung cancer, reflecting a potent modality for overcoming resistance and enhancing the efficacy of immunotherapies.
Mechanism of Action
VHH-P817 exerts its action through simultaneous inhibition of immune checkpoint interactions between CD274 and PDCD1LG2 and their receptors on T cells. Blocking these pathways can restore and amplify the anti-tumor immune response by preventing T cell inhibition and promoting immune-mediated tumor destruction. As a bispecific immune checkpoint inhibitor, VHH-P817 is designed to target both CD274 and PDCD1LG2, thus overcoming potential compensatory mechanisms that limit the efficacy of monospecific agents. The unique nanobody-based structure allows for versatility, potentially supporting further development into antibody-drug conjugates or multi-specific formats, further expanding its applicability across diverse oncological indications.
Lung Cancer
Lung cancer represents a leading cause of cancer-related morbidity and mortality worldwide, accounting for a substantial portion of global cancer cases. The majority of lung cancer diagnoses occur at advanced stages, limiting curative options and contributing to a poor overall prognosis. Standard modalities include surgery, radiation therapy, chemotherapy, and more recently, targeted therapies and immunotherapies. While these advancements have improved outcomes for selected patient subgroups, resistance mechanisms and heterogeneity in tumor biology continue to present significant obstacles. Many patients ultimately relapse or develop refractory disease, underscoring unmet clinical needs for more effective and durable treatment strategies. Novel therapeutics like VHH-P817, which target CD274 and PDCD1LG2-mediated immune evasion, aim to enhance antitumor immunity and address existing therapeutic gaps in the management of lung cancer.