Innovative Bispecific Nanobody Targeting LY6G6D and TNFRSF9 for Advanced Colorectal Cancer Immunotherapy

VHH-P793 is a cutting-edge, fully human nanobody-based therapeutic candidate designed to target both lymphocyte antigen 6 family member G6D (LY6G6D) and TNF receptor superfamily member 9 (TNFRSF9). This bispecific construct harnesses the precision of human monoclonal antibody engineering and the flexibility of single-domain antibody technology. Currently in the Biological Testing stage, VHH-P793 holds significant promise for the treatment of colorectal cancer by modulating immune pathways critical to tumor progression. Combining these two validated immuno-oncology targets, VHH-P793 aims to deliver enhanced anti-tumor activity and provide new hope for patients with colorectal cancer.

Licensing Opportunity

VHH-P793 is available for out-licensing and strategic partnership opportunities. Organizations seeking to expand their oncology or immunotherapy pipeline are invited to collaborate in advancing this promising, fully human bispecific nanobody program towards clinical development and commercialization.

Development Phase

Modality

VHH-P793 is an agonistic, tetravalent, bispecific antibody fusion construct composed of a fully human monoclonal antibody framework that targets LY6G6D, with each heavy chain C-terminus fused to single-domain nanobodies recognizing TNFRSF9. The single-domain antibody format confers a reduced molecular size and high tissue penetration, facilitating access to tumor sites that are less accessible to conventional IgG antibodies. This modular, tetravalent design supports simultaneous engagement of two distinct immunological targets, enhancing immune activation against tumor cells. The structural stability and potential for reduced immunogenicity of humanized nanobodies further support their suitability for overcoming the microenvironmental barriers within colorectal cancer.

Target

LY6G6D and TNFRSF9 are crucial immunological molecules involved in the regulation of immune cell activation and tumor immunogenicity. LY6G6D, a surface antigen expressed on subsets of immune and tumor cells, is implicated in tumor progression pathways in colorectal cancer. TNFRSF9, also known as CD137 or 4-1BB, is a member of the tumor necrosis factor receptor superfamily and is primarily found on activated T cells and natural killer cells. Activation of TNFRSF9 is widely recognized for its role in enhancing anti-tumor immune responses. The co-targeting of LY6G6D and TNFRSF9 by VHH-P793 addresses both tumor cell antigenicity and immune cell co-stimulation, providing a strategic advantage for inducing durable anti-tumor immunity. The bispecific format allows VHH-P793 to simultaneously block tumor escape mechanisms associated with LY6G6D and promote immune activation via TNFRSF9, maximizing therapeutic potential in colorectal cancer.

Mechanism of Action

VHH-P793 exerts a dual mechanism by engaging both LY6G6D on tumor cells and TNFRSF9 on immune effector cells. The anti-LY6G6D moiety directs the nanobody construct toward tumor-associated antigens, while the TNFRSF9 agonistic single-domain antibodies activate costimulatory signaling pathways in T cells. This dual targeting translates into selective recruitment and activation of immune cells within the tumor microenvironment, enhancing cytotoxic T cell function against malignant cells. By acting as a T-cell engager and modulator of signal transduction, VHH-P793 holds potential for robust anti-tumor responses. Furthermore, its modular nanobody-based architecture offers extensibility into novel formats, such as antibody-drug conjugates or additional bispecific/multispecific platforms, broadening its clinical and commercial utility.

Colorectal Cancer

Colorectal cancer represents one of the highest-burden malignancies worldwide, with incidence rising in both developed and developing regions. The disease encompasses malignant tumors originating in the colon or rectum and often progresses asymptomatically until advanced stages. Current treatment strategies include surgery, chemotherapy, radiation therapy, and molecularly targeted therapies. Despite these options, many patients present with late-stage or metastatic disease, historically associated with limited long-term survival. Key unmet needs remain: durable efficacy, reduced systemic toxicity, and strategies to overcome resistance to existing therapies. The advent of immunotherapies has begun to transform the therapeutic landscape, but only a subset of patients achieve lasting benefits. VHH-P793 addresses these challenges by targeting both tumor-associated and immune costimulatory pathways, presenting a novel approach that may expand the reach and durability of immunotherapy in colorectal cancer. Its profile as a bispecific nanobody construct provides unique advantages in tumor targeting and immune activation, potentially filling critical gaps in standard care.