Innovative Multispecific Nanobody Targeting CD276 and CD3 Complex for Advanced Cancer Immunotherapy

VHH-P714 is a cutting-edge, fully human single-domain antibody construct designed to target both the CD276 molecule (CD276) and the CD3 Complex (T Cell Receptor Complex). Currently in the Biological Testing phase, this program addresses the urgent therapeutic needs in cancer by leveraging these clinically relevant immune targets. The unique bispecific architecture of VHH-P714 enables dual engagement of tumor-associated antigens and T cell activation pathways. This approach shows significant promise to overcome resistance mechanisms observed in conventional cancer therapies, positioning VHH-P714 as a potentially transformative asset in oncology treatment innovation.

Licensing Opportunity

VHH-P714 is available for out-licensing and strategic collaborations. We invite industry partners interested in pioneering next-generation cancer immunotherapies to explore co-development and commercialization opportunities for this high-potential asset.

Development Phase

Modality

VHH-P714 is a sophisticated multispecific nanobody-based modality comprising two complementary polypeptide chains. The first chain features a single-domain antibody (sdAb) targeting B7 homolog 3, fused with a heterodimeric Fc knob, a flexible (G4S)3 linker, an anti-CD3 VH domain, and a tandemly linked second anti-B7H3 sdAb. The second chain provides a heterodimeric Fc hole, a similar (G4S)3 linker, and an anti-CD3 VL domain. This modular design capitalizes on the intrinsic advantages of nanobodies—small molecular size, high stability, and superior tumor tissue penetration—which facilitate effective engagement of deeply located or poorly vascularized cancer cells, and promote improved immune synapse formation for targeted cytotoxicity.

Target

CD276 and CD3 Complex are crucial molecular targets in immuno-oncology. CD276 is an immune checkpoint molecule overexpressed in various tumor types and associated with immune evasion, while the CD3 Complex is a component of the T cell receptor critical for T cell activation and signal transduction. CD276 is predominantly upregulated on tumor cells and tumor vasculature, whereas the CD3 Complex is expressed across all T cells. Targeting CD276 enhances selective anti-tumor responses by disrupting tumor immune suppression, while redirecting T cells via the CD3 Complex enables potent immune cell-mediated cytotoxicity against malignant cells. By simultaneously engaging both CD276 and CD3 Complex, VHH-P714 maximizes anti-cancer immune responses, offering strategic differentiation and elevated relevance for cancer immunotherapy pipelines.

Mechanism of Action

VHH-P714 exerts its effects through simultaneous binding to CD276 and the CD3 Complex. By engaging CD276 on tumor cells, the nanobody antagonizes immune checkpoint signaling pathways and reduces cellular immunosuppression within the tumor microenvironment. Concurrently, the anti-CD3 domains recruit and activate T cells by cross-linking them with CD276-positive tumor cells, thereby facilitating efficient immune synapse formation and cytotoxic granule release. This dual action results in enhanced tumor cell lysis and robust immune-mediated anti-tumor effects. Furthermore, the modular structure of VHH-P714 lends itself to broader applications within the nanobody platform, such as the development of antibody-drug conjugates (ADCs) and other multispecific therapeutics.

Cancer

Cancer encompasses a diverse group of diseases characterized by uncontrolled cell proliferation and the potential to invade or metastasize to distant organs. Globally, cancer is a leading cause of mortality, impacting millions each year across heterogeneous populations. Current standard-of-care therapies include surgery, radiation, cytotoxic chemotherapy, immune checkpoint inhibitors, and molecularly targeted agents. While these modalities have improved patient outcomes, many cancers remain resistant or relapse due to intrinsic or acquired mechanisms. There remains a substantial unmet need for therapeutics that can effectively activate immune responses and eradicate residual malignant cells with minimal off-target toxicity. VHH-P714 offers a promising approach by harnessing dual-targeting of CD276 and CD3 Complex, aiming to enhance specificity, boost immune-mediated clearance of tumors, and overcome adaptive resistance pathways that undermine current immunotherapies.