Transforming Cancer Treatment with Bispecific Nanobody Targeting CD47 and LAG3
VHH-P671 is a humanized nanobody-based bispecific monoclonal antibody designed to target both CD47 molecule (CD47) and lymphocyte activating 3 (LAG3). Currently in the Biological Testing phase, VHH-P671 leverages the ability to simultaneously engage two critical immune checkpoints implicated in cancer progression. By inhibiting both CD47 molecule (CD47) and lymphocyte activating 3 (LAG3), VHH-P671 aims to enhance immune-mediated tumor clearance and potentially address resistance mechanisms observed in monotherapy. This innovative approach positions VHH-P671 as a promising candidate for the treatment of cancer.
| Candidate | VHH-P671 |
| Target | CD47 molecule (CD47) lymphocyte activating 3 (LAG3) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P671 is available for out-licensing and strategic collaboration. We welcome discussions with partners interested in advancing innovative immuno-oncology therapeutics to address unmet medical needs in cancer.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P671 |
Modality
VHH-P671 deploys a bispecific monoclonal antibody modality comprised of two polypeptide chains. The first chain features a single domain antibody (nanobody) targeting cytotoxic T lymphocyte-4, engineered onto the heavy chain of an anti-CD47 antibody via a flexible G9-linker. The second chain comprises the anti-CD47 light chain. Expressed in Chinese hamster ovary cells, this design preserves the nanobody’s hallmark properties: low molecular weight, monomeric structure, and enhanced stability. These features translate to superior tissue penetration and the possibility for efficient tumor targeting in the complex microenvironment of cancer. The streamlined molecular format may also reduce immunogenicity while supporting manufacturing versatility.
Target
CD47 and LAG3 are both key immune checkpoint molecules with well-documented roles in oncology. CD47, a transmembrane protein widely expressed on normal and malignant cells, transmits "don’t eat me" signals to macrophages, allowing tumor cells to evade phagocytosis. LAG3 is an inhibitory receptor found primarily on activated T cells and certain other immune subsets, where it dampens anti-tumor immunity through negative regulation of T cell activation. Both CD47 and LAG3 are often upregulated in cancer, contributing to immune escape. By targeting CD47 and LAG3, VHH-P671 offers a strategic advantage for robust antitumor responses, addressing two complementary mechanisms of immune evasion and broadening therapeutic reach within the cancer immunotherapy landscape.
Mechanism of Action
VHH-P671 exerts its therapeutic effect by simultaneously binding CD47 and LAG3, thereby blocking two critical immune checkpoints. Inhibiting CD47 disrupts the interaction between tumor cells and tumor-associated macrophages (TAMs), promoting phagocytosis and innate immune clearance of cancer cells. Concurrently, antagonism of LAG3 releases the brakes on activated T lymphocytes, enhancing adaptive immune responses against tumors. This bispecific approach aligns with the broader strategy of immune checkpoint inhibition and TAM modulation for cancer therapy. Additionally, the nanobody platform incorporated in VHH-P671 provides opportunities for future expansion, such as development of antibody-drug conjugates (ADCs) or trispecific formats targeting additional pathways.
Cancer
Cancer encompasses a diverse group of diseases characterized by the uncontrolled growth and spread of abnormal cells, constituting a leading cause of morbidity and mortality worldwide. The global burden of cancer continues to rise with millions of new diagnoses annually. Standard treatments—such as surgical resection, radiotherapy, chemotherapy, and targeted therapies—have improved survival rates in many cancers but are often limited by toxicity, resistance, and variable efficacy across tumor types and patient populations. Immunotherapies, including immune checkpoint inhibitors, have revolutionized outcomes for some patients yet face challenges like primary or acquired resistance. There remains a significant need for novel immunomodulatory strategies that overcome current barriers to durable remission. VHH-P671, by antagonizing both CD47 and LAG3, could potentially enhance anti-tumor immune activity and offer therapeutic benefit across a broad range of malignancies, addressing critical gaps in the present cancer treatment paradigm.