Innovative Bispecific Nanobody Targeting CD3 Complex and LILRB4 for Acute Myeloid Leukemia Therapy

VHH-P797 is an advanced humanized nanobody-based therapeutic candidate designed to engage CD3 Complex (T Cell Receptor Complex) and leukocyte immunoglobulin like receptor B4 (LILRB4). Currently in the Biological Testing phase, this program leverages the specificity and modularity of single-domain antibody engineering to address the critical medical need in acute myeloid leukemia. By precisely targeting both T cells and leukemia-associated antigens, VHH-P797 provides a promising approach for immunotherapeutic intervention in this aggressive malignancy.

Licensing Opportunity

VHH-P797 is available for licensing and collaboration opportunities. We welcome partnerships to advance this novel bispecific nanobody program for the treatment of acute myeloid leukemia.

Development Phase

Modality

VHH-P797 is a bispecific T-cell engager antibody fusion construct, comprising two polypeptide chains. The first chain features a single-domain antibody (nanobody) targeting LILRB4 fused to a human IgG hole Fc, while the second chain integrates an antigen-binding fragment directed against CD3, fused to a human IgG knob Fc. The single-domain nanobody structure ensures high stability, compactness, and enhanced tumor penetration. These biophysical advantages are particularly well-suited to overcoming the heterogenous and infiltrative nature of acute myeloid leukemia, potentially improving efficacy and pharmacokinetics compared to conventional antibodies.

Target

CD3 Complex and LILRB4 represent two strategically important targets for immunotherapy in acute myeloid leukemia. CD3 Complex is a critical signaling molecule of T cells, essential for immune activation and cytotoxic function, predominantly expressed on T lymphocytes. LILRB4 is an inhibitory receptor expressed mainly on myeloid-derived cells, including monocytic leukemia subsets. CD3 Complex engagement ensures robust T cell activation, while dual targeting of LILRB4 enables selective engagement with leukemic cells, reducing off-target effects. The use of VHH-P797 to target both CD3 Complex and LILRB4 addresses tumor immune evasion and promotes selective anti-leukemic activity, underscoring its value as an innovative immunotherapeutic asset.

Mechanism of Action

VHH-P797 operates as a bispecific T-cell engager, simultaneously binding to CD3 Complex on T cells and LILRB4 on leukemia cells. This dual engagement effectively redirects and activates cytotoxic T lymphocytes towards LILRB4-expressing cells, facilitating targeted destruction of malignant populations. By bridging the T cell/CD3 Complex with leukemia-associated LILRB4, VHH-P797 induces potent immunologic synapse formation, leading to robust and selective cell-mediated cytotoxicity. The single-domain nanobody platform further offers adaptability for developing advanced derivatives such as antibody-drug conjugates or additional bispecific formats, broadening future clinical applications in oncology.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically heterogeneous hematological malignancy characterized by the rapid proliferation of immature myeloid cells in bone marrow and peripheral blood. AML accounts for a significant proportion of adult leukemias, with a global incidence that underscores its importance as a major health burden. Current first-line treatments include intensive chemotherapy and, in eligible patients, hematopoietic stem cell transplantation. While targeted therapies and immunotherapies are emerging, many patients relapse or suffer from refractory disease due to tumor heterogeneity and immune evasion. There is a pressing need for novel strategies that enhance treatment specificity and efficacy. Targeting both CD3 Complex and LILRB4 with a bispecific nanobody like VHH-P797 holds the potential to address key unmet needs by recruiting effector immune cells directly to leukemic blasts, aiming for potent anti-tumor effects with minimized systemic toxicity.