Innovative Bispecific Nanobody Solution Targeting CCR8 and CTLA4 for Bladder Cancer Immunotherapy
VHH-P305 is a fully humanized bispecific nanobody therapeutic candidate designed to target both C-C motif chemokine receptor 8 (CCR8) and cytotoxic T-lymphocyte associated protein 4 (CTLA4). Currently in the biological testing development stage, VHH-P305 leverages advanced antibody engineering to enhance immune-mediated anti-tumor activity for the treatment of bladder cancer. By simultaneously engaging CCR8 and CTLA4, VHH-P305 holds promise for overcoming tumor immune evasion mechanisms and offers a novel immunotherapeutic approach for patients with bladder cancer, a disease with substantial unmet medical needs.
| Candidate | VHH-P305 |
| Target | C-C motif chemokine receptor 8 (CCR8) cytotoxic T-lymphocyte associated protein 4 (CTLA4) |
| Modality | humanized bispecific VHH |
| Indication | Bladder Cancer |
Licensing Opportunity
VHH-P305 is available for out-licensing and collaborative partnerships. We welcome inquiries from experienced biopharmaceutical companies interested in advancing cutting-edge bispecific nanobody immunotherapies in oncology.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P305 |
Modality
VHH-P305 is an afucosylated, bispecific IgG1 antibody featuring two identical polypeptide chains. Each chain comprises an antibody-binding domain targeting CCR8, fused via a flexible (G4S)2 linker to a nanobody domain against CTLA4, followed by connection to an optimized, afucosylated Fc region. This robust molecular architecture results in a single-domain nanobody component, conferring a small molecular size and exceptional stability. The modular format enables deep tumor tissue penetration, improved pharmacokinetics, and effective immune cell engagement. Afucosylation further augments effector function. These unique structural features give VHH-P305 a significant advantage for treating bladder cancer, particularly in reaching the tumor microenvironment and mediating potent immune responses.
Target
CCR8 and CTLA4 are critical immunoregulatory proteins implicated in bladder cancer progression. CCR8, a G protein-coupled receptor, is predominantly expressed on certain T cell subsets, including tumor-infiltrating regulatory T cells in the tumor microenvironment. CTLA4 is an immune checkpoint receptor highly expressed on activated T cells, functioning to downregulate immune responses. Both CCR8 and CTLA4 are overrepresented in the suppressive cellular networks within bladder cancer tissues. Targeting CCR8 can deplete immunosuppressive cell populations, while dual inhibition with CTLA4 can further unleash anti-tumor immunity. The strategic dual engagement of CCR8 and CTLA4 with VHH-P305 positions this therapy with strong potential for disrupting tumor immune tolerance, representing a valuable asset in the bladder cancer immunotherapy landscape.
Mechanism of Action
VHH-P305 exerts its action by concurrently engaging and blocking CCR8 and CTLA4 on immune cell surfaces, thereby functioning as an immune checkpoint inhibitor. Binding to CCR8 on regulatory T cells promotes immune cell depletion within the tumor microenvironment, indirectly enhancing cytotoxic T lymphocyte responses. Simultaneous targeting of CTLA4 relieves inhibition of effector T cells, fostering a robust anti-tumor immune response. The bispecific nanobody design enables simultaneous modulation of key immunosuppressive pathways. Additionally, the modular nanobody-based format offers flexibility for future pipeline developments, such as antibody-drug conjugates (ADCs) or next-generation bispecific constructs, broadening the platform’s potential against bladder cancer and other malignancies.
Bladder Cancer
Bladder cancer is a clinically significant malignancy with a high recurrence rate and substantial global incidence, affecting both men and women, especially in aging populations. Standard treatments include surgical resection, chemotherapy, and radiotherapy, often complemented by immunotherapy or targeted therapy in advanced stages. However, responses to current therapies can be unpredictable, and many patients face disease progression or relapse. The tumor immune microenvironment plays a critical role in resistance to therapy, highlighting the need for innovative immune-based treatments. Despite recent advances, effective, durable immunomodulation remains a key unmet need. VHH-P305, by simultaneously inhibiting CCR8 and CTLA4, offers the potential to overcome tumor immune evasion and improve long-term clinical benefit for patients with bladder cancer.