NKp46 based NKCE Platform for NK Cell Engagement

NKCEs represent an innovative class of immunotherapeutic agents that selectively bridge NK cells with tumor cells, thereby activating potent NK-mediated cytotoxicity against cancer. Creative Biolabs' NKp46-based NKCE Platform for NK Cell Engagement is engineered to precisely direct NK cell activity toward tumor antigens. Targeting NKp46 offers distinct advantages, including sustained receptor expression in the tumor microenvironment, avoidance of CD16α-related limitations such as polymorphism and activation-induced shedding, and high NK-specificity that reduces off-target effects. Our NKp46-based NKCEs provide you with customizable, multifunctional biologics that enhance immune synapse formation, improve tumor infiltration, and support the development of effective, off-the-shelf cancer immunotherapies.

Introduction

NKCEs represent an emerging class of immunotherapeutic agents that function by simultaneously targeting activating receptors on NK cells and tumor-associated antigens on cancer cells. This bispecific engagement effectively bridges NK cells with tumor cells, leading to specific activation of NK cell-mediated cytotoxicity. Among these, NKp46-based NKCEs constitute a distinct category of engineered multifunctional proteins designed to specifically engage NKp46, an activating receptor on NK cells, and direct cytotoxic activity against malignant cells. Compared to conventional CD16a-targeting NKCEs, NKp46-directed constructs offer several advantages, including Fc-independent activation, stable receptor expression within the tumor microenvironment, and resistance to activation-induced downregulation. These features collectively contribute to the potential for sustained NK cell-mediated antitumor activity in tumor tissues.

Fig.1 Current landscape in NK cell engager format development.¹

NKp46-based NKCE Platform for NK Cell Engagement at Creative Biolabs

Creative Biolabs' NKp46-based NKCE Platform for NK Cell Engagement leverages the potent signaling capacity of NKp46 to achieve superior NK cell activation, driving enhanced tumoricidal activity and robust cytokine production. Through tumor antigen-specific engagement, our platform enables precise redirection of NK cells to malignant targets while minimizing off-tumor toxicity. Furthermore, the intrinsic safety profile of NK cell-based therapies significantly reduces risks of cytokine release syndrome (CRS) and neurotoxicity commonly associated with T cell-directed modalities, offering a clinically favorable therapeutic window for solid and hematological malignancies.

What We Can Offer

Our platform provides a comprehensive suite of NKCE development services, spanning from single-domain antibody engineering and multi-specific molecule design to Fc optimization and solid tumor targeting, in order to create highly potent and specific NK cell engagers with validated efficacy.

Our Service Process

Required starting materials:

• Target Antigen Information: Sequence, domain structure, and expression profile on tumor cells.
• Desired Multi-Specificity: Specific requirements for cytokine inclusion, co-stimulatory targets, or other safety elements.
• Initial Lead Scaffolds (Optional): Existing IgG domains, or antigen-binding fragments that you wish to integrate.

Final Deliverables:

• Optimized NKCE gene sequence and expression plasmid.
• Detailed biophysical data and manufacturability assessment.

Key Advantages

• Integrated Modular Engineering Platform: Our core advantage is built on a purpose-designed modular engineering platform that enables seamless integration of targeting, cytotoxic, and immune-boosting functionalities within a single, structurally stable molecule.
• Tailored Molecular Design: We provide end-to-end engineering services from target validation to clinical trials, delivering de-risked candidates precisely configured for your tumor antigen profile and multi-specific format requirements.
• Modularity-Driven Biologics Platform: We integrate targeting, effector, and enhancer functions into unified molecules using small modular components, enabling high stability, simplified production, and multifunctional activity.

FAQ

Why Choose Us?

By combining tumor antigen-specific binding domains with the intrinsic activation capacity of NKp46, our NKCE constructs enable precise redirection of NK cell-mediated killing while maintaining favorable safety profiles distinct from T cell-based therapies. Our platform supports the development of multi-specific, multifunctional biologics suitable for a range of hematological and solid tumor indications, offering a novel and clinically differentiated path to harness innate immunity against cancer.

Customer Reviews

"Using Creative Biolabs' NKp46-based NKCE Platform in our research has significantly improved the biophysical stability of our novel trifunctional construct, which displayed PK properties comparable to a full IgG antibody, minimizing our CMC risk."— Dr. A**a N**e.

"Creative Biolabs' NKp46-based NKCE Platform has significantly facilitated our ability to target CD123+ AML blasts, successfully overcoming the ADCC resistance conferred by high CD64 expression and delivering superior killing potency in in vitro models."— Dr. L**c J**s.

"The scaffold Creative Biolabs provided for was incredibly stable and easy to reformat. This facilitated rapid testing of different valencies, reducing our protein expression costs and significantly accelerating our lead optimization timeline."— Dr. Ana Km.

How to contact us?

Partner with us to mitigate development risks and advance a differentiated immunotherapy candidate for your oncology pipeline. Connect with our team to explore program-specific strategies.

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Reference

1. Zhang, Minchuan et al. "Natural Killer Cell Engagers (NKCEs): a new frontier in cancer immunotherapy." Frontiers in immunology vol. 14 1207276. Distributed under Open Access License CC BY 4.0, without modification. https://doi.org/10.3389/fimmu.2023.1207276.