Dual Targeting Nanobody Therapeutic for Enhanced Cancer Immunotherapy: Simultaneous Inhibition of CD274 and KLRC1

VHH-P611 is a humanized recombinant bispecific nanobody designed to target both CD274 molecule (CD274) and killer cell lectin like receptor C1 (KLRC1). This innovative therapeutic candidate is currently undergoing biological testing and holds promising potential for the treatment of various forms of cancer. By leveraging its dual-target approach, VHH-P611 aims to address key immune evasion mechanisms exploited by tumors. The integration of cutting-edge antibody engineering and a nanobody platform confers specificity and flexibility required for next-generation cancer interventions, supporting its potential as a first-in-class immunotherapeutic asset.

Licensing Opportunity

VHH-P611 is open for out-licensing and collaborative partnerships. Interested parties are invited to explore co-development and commercialization opportunities for this cutting-edge bispecific antibody in the oncology field.

Development Phase

Modality

VHH-P611 is a recombinant bispecific antibody that combines a humanized monoclonal IgG4 targeting KLRC1 with a single domain nanobody directed against CD274, linked together via a flexible (G4S)4 peptide and expressed in Chinese hamster ovary cells. The nanobody component endows the molecule with reduced size and increased tissue penetration while maintaining desirable pharmacokinetics associated with IgG formats. This unique configuration not only enables concurrent blockade of two distinct immunosuppressive pathways in cancer, but also enhances stability and manufacturability, making VHH-P611 a versatile and scalable option for cancer therapy.

Target

CD274 and KLRC1 are pivotal molecules involved in the regulation of immune responses in cancer. CD274 is a membrane protein commonly expressed on tumor cells and activated immune cells, serving as a critical immune checkpoint that suppresses T cell function. KLRC1 is a receptor predominantly expressed on natural killer cells and some T cell populations, acting as an inhibitory modulator that limits immune cell cytotoxicity. Both CD274 and KLRC1 are implicated in the development of immune resistance in cancer. Dual targeting of CD274 and KLRC1 interrupts two major signaling axes used by tumors to evade immune destruction. VHH-P611’s strategy of engaging both CD274 and KLRC1 delivers a compelling therapeutic rationale, addressing intra-tumoral heterogeneity and adaptive resistance mechanisms in oncology.

Mechanism of Action

VHH-P611 exerts its anti-cancer effect by simultaneously blocking CD274 and KLRC1. By inhibiting CD274, an immune checkpoint ligand, VHH-P611 unleashes T-cell mediated anti-tumor immunity. Concurrently, antagonism of KLRC1 on effector immune cells reduces inhibitory signaling, further augmenting cytotoxic responses against malignant cells. This dual checkpoint blockade interrupts tumor-mediated immune suppression on multiple levels, enhancing immune recognition and destruction of cancer cells. Additionally, the nanobody platform incorporated in VHH-P611 offers expandability to additional antibody-based therapeutic formats, such as antibody-drug conjugates or multi-specific biologics, broadening its potential utility across oncology indications.

Cancer

Cancer remains among the leading causes of morbidity and mortality worldwide, with incidence continuing to rise due to population aging and lifestyle changes. Standard cancer treatments include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. While immuno-oncology has transformed cancer management, many patients still experience limited long-term benefits due to intrinsic or acquired immune resistance and tumor heterogeneity. Existing therapies often face challenges such as poor tissue penetration, toxicity, and incomplete checkpoint inhibition. VHH-P611, by targeting both CD274 and KLRC1, addresses these critical gaps by disrupting multiple immunosuppressive pathways simultaneously and enhancing immune cell infiltration into tumor tissue. This dual-target nanobody approach has the potential to improve response rates and durability in diverse cancer types, offering a promising path toward more effective and tailored cancer immunotherapy.