Innovative Bispecific Nanobody Targeting CD22 and FCGR3A for B-Cell Acute Lymphocytic Leukemia Therapy

VHH-P370 is a novel humanized nanobody-based bispecific antibody designed to simultaneously target CD22 molecule (CD22) and Fc gamma receptor IIIa (FCGR3A). Currently in the Biological Testing development stage, VHH-P370 offers a promising strategy for the treatment of B-cell Acute Lymphocytic Leukemia. By leveraging its dual specificity and engineered Fc domain, the program aims to engage distinct immune mechanisms and mediate potent anti-leukemic activity. Its unique construct positions it as a next-generation biologic with potential to address significant unmet needs in hematological malignancies.

Licensing Opportunity

VHH-P370 is currently available for out-licensing. We welcome collaborations with partners who wish to advance innovative therapies for B-cell malignancies through co-development or licensing agreements.

Development Phase

Modality

VHH-P370 is a hetero-dimeric bispecific antibody composed of a Bactrian camel-derived anti-CD22 nanobody and an anti-human CD16A nanobody, connected via glycine-serine linkers and fused to a human Fc domain. Expressed in HEK293T cells, its nanobody architecture features single-domain, small molecular weight modules that afford high tissue penetrability and stability. This modular design ensures effective targeting of malignant B cells in B-cell acute lymphocytic leukemia by maximizing immune synapse formation and promoting effector engagement. The use of a human Fc domain further enhances immune recruitment and half-life, offering distinct competitive advantages for clinical translation in complex hematological environments.

Target

CD22 is a sialoglycoprotein expressed predominantly on the surface of mature B cells and is implicated in the regulation of B cell activation, survival, and apoptosis. FCGR3A is a receptor primarily found on natural killer cells and certain subsets of macrophages, mediating antibody-dependent cellular cytotoxicity (ADCC) and immune modulation. The co-targeting strategy of CD22 and FCGR3A is grounded in strong biological rationale: CD22 is frequently overexpressed in B-cell acute lymphocytic leukemia, making it an established diagnostic and therapeutic marker, while FCGR3A engagement enhances NK-cell mediated killing. By specifically addressing CD22 on malignant cells and FCGR3A on immune effectors, VHH-P370 leverages dual mechanisms to achieve strategic anti-tumor responses and positions itself as a differentiated therapeutic asset in the field.

Mechanism of Action

VHH-P370 engages CD22 on malignant B cells and FCGR3A on effector immune cells, effectively bridging these populations to induce cytotoxic immune responses. The nanobody binds specifically to CD22, facilitating selective recognition of leukemic cells, while simultaneous interaction with FCGR3A activates natural killer cells and promotes robust antibody-dependent cellular cytotoxicity (ADCC). This dual engaging capability enables potent immune synapse formation and targeted cell lysis. Furthermore, the modular nature of the nanobody platform supports the development of advanced therapeutic formats such as bispecifics and antibody-drug conjugates (ADCs), expanding future opportunities in the immuno-oncology landscape.

B-cell Acute Lymphocytic Leukemia

B-cell acute lymphocytic leukemia (ALL) is a hematologic malignancy arising from the uncontrolled proliferation of immature B lymphoid cells in the bone marrow and peripheral blood. It predominantly affects children but can also occur in adults and is characterized by rapid disease progression and significant relapse rates. Standard therapeutic approaches include intensive chemotherapy regimens, hematopoietic stem cell transplantation, and emerging targeted or cellular immunotherapies. Despite therapeutic advances, many patients contend with drug resistance, relapse, or therapy-associated toxicities, underscoring urgent unmet clinical needs. Novel agents that can selectively target malignant B cells while enhancing the host immune response are in high demand. By precisely engaging CD22 and immune effectors via FCGR3A, VHH-P370 offers a promising strategy to improve disease control and outcome in patients with B-cell acute lymphocytic leukemia.