Innovative Bispecific Nanobody Targeting CD3 Complex and MSLN for Advanced Breast Cancer Immunotherapy

Innovative Bispecific Nanobody Targeting CD3 Complex and MSLN for Advanced Breast Cancer Immunotherapy

VHH-P367 is a fully humanized nanobody-inspired bispecific antibody targeting the CD3 Complex (T Cell Receptor Complex) and mesothelin (MSLN). Currently in the Biological Testing stage, VHH-P367 is strategically engineered to address the unmet medical needs in Breast Cancer therapy. By simultaneously targeting CD3 Complex (T Cell Receptor Complex) present on T cells and MSLN frequently overexpressed on malignant cells, this molecule offers a novel approach with the potential to enhance antitumor immunity and specificity in breast cancer treatment.

CandidateVHH-P367
TargetCD3 Complex (T Cell Receptor Complex)
mesothelin (MSLN)
Modalityhumanized bispecific VHH
IndicationBreast Cancer

Licensing Opportunity

VHH-P367 is now open for partnering and out-licensing opportunities. We welcome inquiries from biopharmaceutical companies and collaborative partners interested in next-generation immuno-oncology assets targeting CD3 Complex and MSLN for breast cancer.

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Development Phase

Program Research Preclinical Phase 1
VHH-P367

Modality

VHH-P367 employs a sophisticated bispecific antibody construct composed of two polypeptide chains: an anti-CD3 light chain component and an anti-CD3 heavy chain fused to an IgG1 mutant constant region, further linked to an alpaca-derived single domain antibody against human mesothelin via a (G4S)3 flexible linker. Expression in Chinese hamster ovary cells ensures robust production and optimal folding. The nanobody structure provides advantages such as reduced molecular weight, enhanced tissue penetration, and improved stability, offering promise for targeting solid tumors like breast cancer where deep tissue accessibility and immune cell engagement are critical.

Target

CD3 Complex is a crucial component of the T cell receptor machinery, primarily expressed on mature T lymphocytes and orchestrating T cell activation. MSLN is a cell surface glycoprotein highly expressed in multiple malignancies, including breast cancer, while showing limited presence in normal tissues. Both CD3 Complex and MSLN serve as strategic targets in oncology: targeting CD3 Complex enables direct activation and recruitment of T cells, and targeting MSLN facilitates tumor specificity due to its preferential overexpression in cancer cells. By dually engaging CD3 Complex and MSLN, VHH-P367 integrates immune cell redirection toward tumor cells, aligning with contemporary approaches in cancer immunotherapy and enabling enhanced precision against breast cancer.

Mechanism of Action

VHH-P367 operates by concurrently binding to CD3 Complex on T cells and MSLN on tumor cells. This dual engagement leads to the formation of a cytolytic synapse, triggering T cell activation through signal transduction modulation and facilitating targeted tumor cell lysis. The nanobody format offers additional benefits, including high stability and reduced immunogenicity, positioning VHH-P367 for versatile applications such as bispecific T cell engagers (BiTE) or as the basis for antibody-drug conjugate (ADC) development. Through signal transduction modulation, VHH-P367 amplifies the specificity and magnitude of the anti-tumor immune response, showing promise as an innovative treatment strategy for breast cancer.

Breast Cancer

Breast cancer remains one of the most commonly diagnosed cancers worldwide, affecting millions of women and accounting for significant morbidity and mortality. While current treatment paradigms include surgery, chemotherapy, radiation therapy, endocrine therapy, and targeted biologics, challenges such as tumor heterogeneity, metastatic spread, drug resistance, and adverse effects limit effectiveness. Immunotherapies and targeted approaches have improved outcomes for some patients; however, a substantial fraction face recurrent, refractory, or advanced disease where conventional therapies offer limited benefit. Unmet medical needs include more precise tumor targeting, overcoming immune suppression, and reducing systemic toxicity. VHH-P367, by leveraging dual targeting of CD3 Complex and MSLN, holds potential to address these urgencies by harnessing the immune system for specific, powerful, and safer eradication of breast cancer cells.

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