Innovative Bispecific Nanobody Immunotherapy Targeting CD33 and TRDV2 for Acute Myeloid Leukemia

VHH-P241 is a fully humanized nanobody-based bispecific antibody designed to target both CD33 molecule (CD33) and T cell receptor delta variable 2 (TRDV2). Currently in the biological testing stage of development, VHH-P241 holds significant therapeutic potential for the treatment of acute myeloid leukemia. By leveraging the selectivity of nanobody technology, this construct enables precise engagement of malignant myeloid cells and cytotoxic T cells, supporting a dual-targeting strategy with the goal of enhancing anti-leukemic responses while minimizing effects on normal tissues.

Licensing Opportunity

VHH-P241 is available for global out-licensing and strategic collaborations. Partners interested in advancing innovative immunotherapies for hematologic malignancies are welcome to discuss potential development and commercialization opportunities.

Development Phase

Modality

VHH-P241 employs a bispecific antibody fusion construct format, consisting of two nanobody-based arms. One arm targets TRDV2 on Vgamma9Vdelta2 T cells, the other targets human CD33, each fused to engineered IgG1 Fc regions (Fc-knob and Fc-hole) to promote heterodimer formation and functional activity. Expressed in CHO cells, the nanobody domains provide advantages of small molecular size, single-domain structure, and high tissue penetration. These features are particularly beneficial for addressing acute myeloid leukemia, enhancing the capacity to access and eliminate malignant cells even in challenging microenvironments. The fusion design further supports pharmacokinetic stability and flexible modular development.

Target

CD33 and TRDV2 represent clinically established immunological targets for hematologic malignancies. CD33 is a transmembrane sialic acid-binding immunoglobulin-like lectin, mainly expressed on myeloid lineage cells including blasts in acute myeloid leukemia. TRDV2 is a variable region of the T cell receptor highly prevalent on Vgamma9Vdelta2 T cells, a subset of cytotoxic T cells with demonstrated anti-tumor capability. Targeting CD33 enables selective identification and engagement of AML blasts, while engaging TRDV2 harnesses effector T cells for immune-mediated cytotoxicity. The dual targeting capacity of VHH-P241, focusing on both CD33 and TRDV2, represents a strategic innovation for acute myeloid leukemia therapy, maximizing specific anti-leukemic activity and immunomodulation.

Mechanism of Action

VHH-P241 acts as a T cell engager by simultaneously binding to CD33 on leukemic cells and TRDV2 on Vgamma9Vdelta2 T cells. This bispecific interaction facilitates the formation of immunological synapses, promoting targeted cytotoxicity against CD33-positive malignant myeloid cells. The antibody construct exploits the natural ability of TRDV2-expressing T cells to mediate anti-tumor activity, redirecting them specifically to the AML blasts. The nanobody platform underlying VHH-P241's design allows customizable engineering for future generations, such as antibody-drug conjugates or additional bispecific/immune-modulatory architectures, expanding application potential.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by the rapid proliferation of abnormal myeloid progenitor cells in the bone marrow and peripheral blood. AML is among the most common acute leukemias in adults, with significant global incidence and a particularly poor prognosis in relapsed or refractory settings. Standard treatments for AML currently rely on intensive cytotoxic chemotherapy, hematopoietic stem cell transplantation, and, more recently, targeted molecular therapies and immunotherapies. Despite these advances, outcomes remain unsatisfactory due to high relapse rates, toxicity, limited efficacy in certain subpopulations, and lack of durable response. There is a substantial unmet need for more effective and selective therapies that can overcome immune evasion and limit collateral damage. VHH-P241, by targeting both CD33 and TRDV2 to facilitate potent cell-mediated killing of malignant cells, represents a promising candidate for addressing these challenges in AML management.