Innovative Nanobody Targeting MICA and MICB for Next-Generation Cancer Therapeutics
VHH-P553 is a fully humanized nanobody program designed to target MHC class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB). Currently in the Biological Testing phase, VHH-P553 harnesses the unique properties of single-domain antibodies fused with IgG1 Fc regions, significantly enhancing its therapeutic potential. By specifically binding the alpha 3 regions of MICA and MICB, proteins that are commonly overexpressed or shed by cancer cells, VHH-P553 aims to interrupt key immunomodulatory pathways that contribute to tumor immune evasion. This program offers promising opportunities for the treatment of various cancers, leveraging its molecular precision and optimized biological activity.
| Candidate | VHH-P553 |
| Target | MHC class I polypeptide-related sequence A (MICA) MHC class I polypeptide-related sequence B (MICB) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P553 is available for out-licensing and partnership opportunities. We welcome collaborations with industry and academic partners interested in advancing innovative immuno-oncology therapies targeting MICA and MICB.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P553 |
Modality
VHH-P553 is a bivalent single-domain antibody, combining the small size and high stability of nanobodies with the Fc region of human IgG1 to enhance pharmacokinetic properties. Its design targets the alpha 3 domains of both MICA and MICB, maximizing functional coverage and immune effector engagement. The structural features of the nanobody framework allow for superior tissue penetration and stability compared to conventional antibodies, which is particularly advantageous in solid tumors with dense microenvironments. The fusion with constant regions further supports therapeutic efficacy by recruiting immune effector functions, making VHH-P553 a versatile candidate for cancer therapy.
Target
MICA and MICB are stress-inducible proteins belonging to the non-classical MHC class I family. They are primarily expressed on the surface of epithelial cells and are upregulated in many tumor types, including carcinomas. MICA and MICB function as ligands for activating immune receptors on natural killer (NK) and certain T cells, stimulating immune-mediated lysis of abnormal cells. However, tumor cells often exploit shedding or downregulation of MICA and MICB to escape immune surveillance. Targeting MICA and MICB thus represents a rational approach in cancer therapy, as restoring or enhancing their expression can reinvigorate host anti-tumor responses. VHH-P553, with its dual and precise targeting capability for MICA and MICB, is strategically designed to counteract tumor immune evasion and offers a differentiated asset in immuno-oncology pipelines.
Mechanism of Action
VHH-P553 exerts its effect by specifically binding to MICA and MICB on the surface of cancer cells. Through this interaction, VHH-P553 blocks or alters the engagement of these molecules with their corresponding immune receptors, such as NKG2D, on cytotoxic lymphocytes. This can prevent tumor-derived mechanisms that promote immune escape, such as the shedding of MICA and MICB from cell surfaces, thereby preserving or enhancing immune surveillance and cytolytic activity against tumor cells. Thanks to its modular nanobody platform, VHH-P553 can also serve as a foundation for additional therapeutic modalities, including antibody-drug conjugates or bispecific antibodies, broadening its future applications in oncology.
Cancer
Cancer remains one of the leading causes of morbidity and mortality worldwide, encompassing a diverse range of malignant diseases originating from various tissues. Despite significant advances in early detection and therapy, the global burden of cancer continues to rise. Current standard-of-care includes surgery, chemotherapy, radiotherapy, immunotherapies, and targeted agents. However, many patients experience relapse, resistance, or unacceptable toxicity, emphasizing the need for novel modalities with greater efficacy and improved safety profiles. Tumor immune evasion remains a core challenge in achieving durable clinical responses. VHH-P553, by targeting the immunomodulatory molecules MICA and MICB, has the potential to overcome immune escape mechanisms commonly deployed by tumors. This targeted approach may enable enhanced anti-tumor immunity and address significant unmet needs across multiple cancer types.