Next-Generation Bispecific Nanobody Immunotherapy Targeting CD3 Complex and FOLH1 for Metastatic Prostate Cancer

VHH-P780 is a novel, humanized single-domain antibody-based therapeutic candidate specifically designed to target both CD3 Complex (T Cell Receptor Complex) and folate hydrolase 1 (FOLH1). This innovative nanobody construct is currently in the Biological Testing stage and offers promising potential for the treatment of metastatic prostate cancer. By engaging key molecular targets involved in tumor recognition and T cell activation, VHH-P780 aims to address the significant unmet need for effective and selective immunotherapies in advanced prostate cancer.

Licensing Opportunity

VHH-P780 is currently available for out-licensing and collaborative partnerships. We welcome inquiries from industry partners interested in advancing this innovative immunotherapy candidate for metastatic prostate cancer.

Development Phase

Modality

VHH-P780 is a protease-activated T cell engager with a bispecific fusion protein architecture. It consists of an anti-prostate specific membrane antigen humanized single-domain antibody (nanobody) linked in tandem to an anti-CD3 single-chain variable fragment, joined via engineered release sequences, and expressed in Escherichia coli. The inherent advantages of nanobodies, including small molecular size and exceptional stability, allow for deep tumor penetration, high target specificity, and manufacturing efficiency. These qualities enhance the therapeutic potential for challenging indications such as metastatic prostate cancer, where cellular interactions within the tumor microenvironment are critical.

Target

VHH-P780 selectively binds to both CD3 Complex and FOLH1. CD3 Complex is a critical component of the T cell receptor signaling machinery, predominantly expressed on T lymphocytes, and its engagement facilitates T cell activation. FOLH1 is a glutamate carboxypeptidase highly expressed on the surface of prostate cancer cells, especially in metastatic lesions. Targeting both CD3 Complex and FOLH1 enables precise recruitment and redirection of T cells to FOLH1-expressing tumor cells in metastatic prostate cancer. This dual approach leverages the pivotal biological functions of CD3 Complex and FOLH1, providing a strategically attractive therapeutic axis for advancing immuno-oncology solutions in hard-to-treat cancers.

Mechanism of Action

VHH-P780 acts as a bispecific T cell engager by simultaneously binding to FOLH1 on prostate cancer cells and CD3 Complex on T lymphocytes. This proximity-induced activation enables direct redirection of T cell cytotoxicity toward tumor cells, resulting in targeted tumor cell lysis. By focusing immune effector activity through precise engagement of CD3 Complex and FOLH1, VHH-P780 is designed to enhance tumor selectivity and limit off-target immune activation. The single-domain antibody format further supports development potential for nanobody-based bispecifics and can serve as a platform for future innovations in antibody-drug conjugates or multi-targeted immunotherapies.

Metastatic Prostate Cancer

Metastatic prostate cancer is a leading cause of cancer-related morbidity and mortality in men worldwide. This disease is frequently diagnosed at advanced stages, marked by dissemination to bone and soft tissue, which significantly reduces patient survival and quality of life. Standard treatments include androgen deprivation, chemotherapy, and next-generation targeted therapies; however, most patients ultimately develop resistance, leading to progression of metastatic lesions. The existing limitations of current modalities, such as limited durability of response and significant side effects, highlight the urgent need for next-generation, highly selective therapeutics. VHH-P780, by targeting both immune effector mechanisms and tumor-specific antigens, represents a promising strategy to overcome these challenges and address the substantial unmet clinical need in metastatic prostate cancer.