Next-Generation Bispecific Nanobody Targeting CCR8 and TNFRSF1B for Innovative Cancer Therapy

VHH-P421 represents a novel humanized nanobody platform developed as a bispecific antibody fusion construct with dual specificity for the C-C motif chemokine receptor 8 (CCR8) and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B). This investigational asset is currently in the Biological Testing stage and is being evaluated for its potential to address critical needs in cancer treatment. By simultaneously targeting CCR8 and TNFRSF1B, VHH-P421 aims to leverage synergistic mechanisms within the tumor microenvironment, offering a differentiated approach among immuno-oncology therapies. Expression in CHO cells supports scalable manufacturing and therapeutic consistency, positioning VHH-P421 as a promising candidate in the oncology pipeline.

Licensing Opportunity

VHH-P421 is available for out-licensing opportunities. We welcome discussions with industry partners seeking access to innovative immuno-oncology assets or collaboration on the global development of this novel bispecific antibody platform.

Development Phase

Modality

VHH-P421 is engineered as a bispecific antibody fusion construct combining a human monoclonal IgG1 kappa backbone with high specificity toward CCR8 and a single-chain variable fragment designed to target TNFRSF1B. The nanobody element provides a compact, single-domain antibody structure, noted for its small molecular weight and enhanced tissue penetrability compared to conventional antibodies. Its modular fusion design uses optimized linkers to ensure spatial accessibility and functional independence of both binding domains. The use of CHO cell expression systems ensures reliable protein production and post-translational modifications. This multidomain construct offers potential advantages in cancer therapy by enabling simultaneous modulation of distinct tumor-associated pathways, improved tumor infiltration, and reduced immunogenicity, presenting a cutting-edge modality for complex oncology indications.

Target

CCR8 and TNFRSF1B are pivotal surface receptors implicated in tumor progression and immune modulation. CCR8, a chemokine receptor, is primarily expressed on specific subsets of immune cells such as regulatory T cells (Tregs) that infiltrate tumors, playing a key role in immunosuppressive microenvironments. TNFRSF1B, another important member of the tumor necrosis factor receptor family, is found on immune cells and some tumor cells; it modulates cell survival, proliferation, and immune regulation. Targeting CCR8 is a strategy to disrupt Treg-mediated suppression in tumors, potentially enhancing anti-tumor immunity. Meanwhile, inhibiting or modulating TNFRSF1B can interfere with survival and proliferation signals supporting tumor growth. The combination of CCR8 and TNFRSF1B as dual targets positions VHH-P421 for strategic value in the immuno-oncology landscape, enabling it to address multiple mechanisms underlying cancer resistance and tumor immune evasion. Engaging both CCR8 and TNFRSF1B underpins VHH-P421’s differentiated clinical potential.

Mechanism of Action

VHH-P421 exerts its antitumor effects through dual engagement with CCR8 and TNFRSF1B, acting as a targeted signal transduction modulator within the tumor microenvironment. By binding CCR8, VHH-P421 may reduce the suppressive function and accumulation of regulatory T cells, thereby restoring anti-tumor immune responses. Concurrent action on TNFRSF1B can disrupt signaling pathways that promote tumor cell survival and proliferation, or reprogram immune responses. The bispecific nanobody format enables simultaneous disruption of two critical pathways involved in tumor immune evasion and persistence. The underlying nanobody technology also offers versatility for the generation of additional multispecific constructs or conjugates, such as antibody-drug conjugates (ADCs) or tailored bispecifics, providing a strong foundation for platform extension across diverse oncology indications.

Cancer

Cancer comprises a group of diseases characterized by uncontrolled cell growth with the potential to invade surrounding tissues and metastasize to distant organs. It is a leading cause of morbidity and mortality worldwide, with rising incidence due to aging populations and lifestyle factors. Standard treatments include surgery, radiation, chemotherapy, targeted therapies, and immunotherapies. Although advances in targeted and immune-based treatments have improved outcomes for some patients, limitations such as tumor heterogeneity, immune suppression, resistance mechanisms, and systemic toxicity persist. Many cancers remain challenging to treat, especially in advanced or refractory stages. There is a critical need for strategies that can effectively modulate the tumor microenvironment, overcome immune escape, and provide durable responses. VHH-P421’s dual-targeted approach against CCR8 and TNFRSF1B offers promising potential by combining selective tumor immune modulation and direct tumor cell targeting, potentially improving therapeutic efficacy and expanding options for patients with difficult-to-treat cancer subtypes.