Innovative Bispecific Nanobody for Dual Targeting of CD3 Complex and ERBB2 in Cancer Therapy

VHH-P358 is a next-generation therapeutic candidate selectively designed to target both the CD3 Complex (T Cell Receptor Complex) and erb-b2 receptor tyrosine kinase 2 (ERBB2). This fully humanized nanobody is currently in the Biological Testing phase and is intended for the treatment of cancer. By engineering affinity for these two pivotal molecules, VHH-P358 aims to harness and direct immune responses specifically towards malignant cells, offering novel prospects in oncology. The strategic engagement of CD3 Complex (T Cell Receptor Complex) on immune effector cells and ERBB2 on cancer cells underpins its therapeutic rationale and distinguishes it as an advanced therapeutic option for malignancies overexpressing ERBB2.

Licensing Opportunity

VHH-P358 is available for licensing and collaborative development. We welcome partnership inquiries from organizations seeking to advance innovative immunotherapy solutions in oncology.

Development Phase

Modality

VHH-P358 is a bispecific T-cell engager (BiTE) based on a fusion construct that combines a humanized single-chain variable fragment (scFv) targeting CD3 with a llama-derived, humanized single-domain antibody (nanobody) against human ERBB2, linked by a flexible G(3GS)2 sequence and expressed in HEK cells with a histidine tag for purification. The nanobody component offers significant structural advantages: its small size allows for improved tissue penetration and tumor accessibility, while the inherent stability and solubility enhance its manufacturability and pharmacological profile. For cancer therapy, this modality enables the effective redirection of cytotoxic T cells to ERBB2-positive tumor cells, potentially overcoming barriers faced by larger, conventional antibodies.

Target

CD3 Complex and ERBB2 are clinically validated targets in oncology. CD3 Complex is a critical component of the T-cell receptor involved in T-cell activation and immune synapse formation, predominantly expressed on T lymphocytes. ERBB2 is a transmembrane receptor tyrosine kinase frequently overexpressed in various cancers, playing a central role in driving cell proliferation and survival. Targeting both CD3 Complex and ERBB2 allows for a dual-function immune mechanism: recruiting T cells via CD3 Complex and selectively recognizing tumor cells via ERBB2. This dual targeting approach positions VHH-P358 with significant strategic value, as it enables precise immune activation against ERBB2-expressing tumor cells by leveraging the cytotoxic activity of T cells through CD3 Complex engagement while minimizing off-target effects.

Mechanism of Action

VHH-P358 exerts its therapeutic action by simultaneously binding to CD3 Complex on T cells and ERBB2 on tumor cells. The bispecific nanobody structure facilitates close proximity between cytotoxic T lymphocytes and ERBB2-positive cancer cells, promoting T-cell activation and targeted cell lysis. By modulating signal transduction and engaging immune effector cells, VHH-P358 acts as both a signal transduction modulator and a T-cell engager. This mechanism enhances the immune system's specificity and cytotoxic response toward malignant tissue. Additionally, the modular design of the nanobody platform opens a broad range of derivative applications, such as antibody-drug conjugates, multi-specific antibodies, and other immune cell engagers, further highlighting its potential to address diverse clinical needs in oncology.

Cancer

Cancer represents a global health challenge with diverse etiologies and significant morbidity and mortality. It encompasses a group of diseases characterized by uncontrolled cell growth and the potential to invade or metastasize to other tissues. Cancer incidence continues to rise worldwide, affecting millions of individuals annually. The current treatment landscape includes surgery, chemotherapy, radiotherapy, immunotherapy, and targeted therapies. Despite advancements, limitations such as toxicity, resistance, recurrence, and limited efficacy in certain subtypes persist. Unmet needs include more specific, less toxic treatments and options for refractory or relapsing disease. VHH-P358, by engaging both CD3 Complex and ERBB2, addresses key gaps by harnessing targeted immune activation and providing potential benefit for cancers overexpressing ERBB2, including those unresponsive to conventional therapies. The unique nanobody-based, bispecific approach may offer enhanced tumor targeting, reduced off-target cytotoxicity, and improved clinical outcomes.