Innovative Bispecific Nanobody Targeting CTLA4 and TIGIT for Next-Generation Cancer Immunotherapy
VHH-P481 is a humanized bispecific nanobody-based IgG1 antibody currently at the Biological Testing stage, developed to target cytotoxic T-lymphocyte associated protein 4 (CTLA4) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). By engaging both CTLA4 and TIGIT, VHH-P481 leverages dual immune checkpoint blockade to potentially enhance anti-tumor immune responses. The molecule’s innovative structure is designed to address a broad range of cancer indications and offers promise as a next-generation immunotherapeutic. Its humanized composition further positions it as a strong candidate for clinical development in oncology.
| Candidate | VHH-P481 |
| Target | cytotoxic T-lymphocyte associated protein 4 (CTLA4) T cell immunoreceptor with Ig and ITIM domains (TIGIT) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P481 is actively available for out-licensing opportunities. We welcome collaboration and partnership inquiries from biopharmaceutical companies seeking to advance innovative immuno-oncology assets.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P481 |
Modality
VHH-P481 utilizes a bispecific IgG1 antibody modality, comprising a humanized anti-TIGIT nanobody fused to a human anti-CTLA4 variable heavy chain and an engineered Fc region for optimized effector function. Nanobodies, characterized by their small molecular size and single-domain structure, offer superior tissue penetrability and good stability compared to conventional antibodies. This modality enables VHH-P481 to target two immune checkpoints simultaneously, which is advantageous for overcoming tumor-induced immune suppression. The compact nanobody component can improve tumor infiltration, potentially leading to enhanced therapeutic efficacy in cancer settings.
Target
CTLA4 and TIGIT are both critical immune checkpoint molecules. CTLA4 is primarily expressed on regulatory T cells and activated T cells, functioning as a negative regulator of T cell activation. TIGIT is predominantly found on T cells and natural killer cells, contributing to immune evasion by tumors. In the context of cancer, upregulation of CTLA4 and TIGIT on lymphocytes enables tumors to dampen immune surveillance and hinder effective anti-tumor responses. Therapeutically targeting both CTLA4 and TIGIT has a strong scientific foundation, as inhibition of these checkpoints can restore immune function and augment tumor cell elimination. VHH-P481’s dual targeting of CTLA4 and TIGIT represents a strategic advance for broad-spectrum cancer immunotherapy and positions it as a highly attractive asset in the immuno-oncology landscape.
Mechanism of Action
VHH-P481 is designed as a dual immune checkpoint inhibitor, simultaneously targeting CTLA4 and TIGIT. By binding CTLA4, VHH-P481 blocks negative signaling pathways that inhibit T cell activation. Concurrently, inhibition of TIGIT prevents suppression mediated by tumor cells and regulatory T cells, further restoring the cytotoxic function of effector lymphocytes. The dual blockade leads to enhanced T cell proliferation and cytokine production, promoting a more vigorous and sustained anti-tumor immune response. This mechanism makes use of the nanobody platform’s versatility, which allows for bispecific formats and potential expansion to include antibody-drug conjugates (ADCs) or other multi-specific constructs in the future, supporting innovation and pipeline diversification.
Cancer
Cancer is a diverse group of diseases characterized by uncontrolled cellular proliferation and the ability to invade surrounding tissues and metastasize to distant organs. Affecting millions of people globally each year, cancer remains a leading cause of morbidity and mortality. Present treatment modalities include surgery, radiation therapy, chemotherapy, targeted small molecules, immunotherapy, and combinations thereof. Despite advances, significant challenges persist, including treatment resistance, toxicity, and disease recurrence. Immune checkpoint inhibitors have revolutionized cancer therapy, harnessing the body's immune system for more effective anti-tumor activity. However, not all patients benefit, and new therapies addressing additional immune escape pathways are urgently needed. VHH-P481, targeting both CTLA4 and TIGIT, offers a novel mechanism that may overcome current limitations, improve patient responses, and expand the reach of immunotherapy to a broader range of malignancies.