Cutting-edge Nanobody-Based T Cell Engager Targeting Both CD3 Complex and TNFRSF9 for Innovative Cancer Immunotherapy
VHH-P578 is a novel, humanized nanobody-based fusion protein designed to engage both CD3 Complex (T Cell Receptor Complex) and TNF receptor superfamily member 9 (TNFRSF9), two critical immune regulatory targets, for the treatment of cancer. Currently in the Biological Testing phase, VHH-P578 employs cutting-edge single domain antibody technology to create a bispecific molecule that harnesses and redirects T cell activity toward malignant cells. By leveraging the unique functionalities of the CD3 Complex and TNFRSF9, this program aims to provide a new class of immunotherapeutic intervention with enhanced precision and potential clinical benefit for a broad range of cancer types.
| Candidate | VHH-P578 |
| Target | CD3 Complex (T Cell Receptor Complex) TNF receptor superfamily member 9 (TNFRSF9) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P578 is available for out-licensing opportunities. We welcome collaboration discussions with partners seeking to advance innovative immuno-oncology assets targeting CD3 Complex and TNFRSF9 for cancer therapy.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P578 |
Modality
VHH-P578 is a bispecific nanobody fusion molecule consisting of two chains: the first incorporates an anti-4-1BB single domain antibody fused to the C-terminus of an anti-CD3 antibody light chain through a flexible (G4S)3 linker, while the second comprises the anti-CD3 heavy chain. The use of single domain antibodies (nanobodies) endows VHH-P578 with benefits such as smaller molecular size, increased stability, and enhanced tissue penetration compared to conventional antibodies. This modular architecture expressed in HEK293F cells supports high expression yields and manufacturing flexibility, contributing to its therapeutic potential especially in solid tumor microenvironments often refractory to traditional monoclonal antibodies.
Target
CD3 Complex and TNFRSF9 are key modulatory components of T cell signaling and activation, making them highly validated targets in immuno-oncology. CD3 Complex is a crucial element of the T cell receptor, expressed predominantly on mature T lymphocytes, and orchestrates antigen-specific immune responses. TNFRSF9 is primarily found on activated T cells and other immune cells and is involved in the co-stimulation and amplification of cytotoxic responses. Modulating both CD3 Complex and TNFRSF9 functions enables robust and controlled immune activation against tumor cells. The dual targeting approach of VHH-P578 leverages the established roles of CD3 Complex in T cell recruitment and TNFRSF9 in T cell proliferation and survival, representing a high-value, strategic asset with significant differentiation for cancer immunotherapy development.
Mechanism of Action
VHH-P578 is engineered to selectively engage the CD3 Complex and TNFRSF9 on T cells, functioning as a T cell engager and immune co-stimulatory modulator. By binding to the CD3 Complex, VHH-P578 initiates T cell receptor signaling, resulting in T cell activation and targeted cytotoxicity against cancer cells. Simultaneous engagement of TNFRSF9 amplifies T cell responses and promotes sustained antitumor immunity. This dual mechanism is designed to overcome immunosuppressive barriers within the tumor microenvironment. Moreover, the nanobody architecture of VHH-P578 facilitates potential expansion into advanced modalities such as bispecific, multispecific, or antibody-drug conjugate formats, supporting versatile applications across next-generation cancer therapies.
Cancer
Cancer encompasses a diverse range of malignant diseases characterized by uncontrolled cellular proliferation and the ability to invade or metastasize to distant organs. Globally, cancer remains a leading cause of morbidity and mortality, with incidence continuing to rise due to aging populations and lifestyle factors. Standard treatment options include surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapies. However, many patients experience limited efficacy, resistance development, or significant adverse effects, underscoring a substantial unmet medical need. Innovative immunotherapies, especially those that harness the patient's own immune system, are reshaping the standard of care but often face challenges such as suboptimal immune activation in certain tumor types. VHH-P578, by targeting both CD3 Complex and TNFRSF9, offers a promising approach to amplify immune responses through dual mechanisms, with the potential to enhance therapeutic efficacy and address gaps in hard-to-treat cancers.