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NKG2D based Multi-target CAR Construction Service

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NKG2D-based Multi-target CAR

Since CAR-T therapy has achieved great success in adoptive immunotherapy of relapse/refractory cancer, many efforts have been taken to improve the safety, effectiveness, and persistence of the cells to treat complex solid tumors. Recently, a multi-target CAR technology has been developed to direct constant CAR-engineered immune cells toward multiple tumors or targets. This functional CAR is designed by introducing a modified NKG2D (mNKG2D) extracellular domain as a ligand-binding domain to the scFV location of a classic CAR molecular. The mNKG2D-CAR expressing cells are activated by the modified NKG2D ligand fused to antigen-specific antibodies and then attracted to the tumor site and perform antigen-specific cytotoxicity. The mNKG2D-mediated CAR-cell therapy is versatile and flexible under the regulation of different antibodies.

Fig.1 NKG2D based cytotoxicity on NK and T cells. (Slavuljica, et al., 2011) Fig.1 NKG2D on NK and T cells mediated cytotoxicity.¹

Service Workflow

The Creative Biolabs workflow is a phased, transparent process designed for speed, quality, and seamless transition to clinical-scale manufacturing.

Workflow of NKG2D-based multi-target CAR construction. (Creative Biolabs Original)

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Service Specifications

mNKG2D Production

Disturb natural NKG2D-ligand interactions.
Introducing mutations in NKG2D.
Binding activity verified by BLI and ELISA assay.

High-affinity Ligand Production

Several rounds of screening.
Specific binding to mNKG2D.
Competitive with natural NKG2D.

Antigen-specific Antibody Generation

Advanced technologies, hybridoma, phage display, etc.
A biobank of validated antibodies available for published antigens.

mNKG2D-CAR Construction and Delivery

mNKG2D CAR vector design and construction.
Viral vectors package and delivery.

Function Tests

We provide multiple downstream services to assess the potency of established CAR constructs.

In Vivo Assay

In Vitro Assay

Fuse Ligand to Antibodies

Conjugate ligands to C-terminal of antibodies.
Disturb antibody intrinsic ADCC activity.

Key Features of the NKG2D-based Multi-target CAR

Recognize More Than One Target
Single and combined multiple antibodies can direct NKG2D CAR-expressing cells to various antigens and avoid antigen loss-induced relapse.
Controllable Safety and Efficacy
The efficacy of the cell therapy is dependent on the dosage of the CAR-T/NK cell and the amounts of antigen-specific antibodies.
Improved Proliferation and Persistence
mNKG2D CAR is a human-derived protein molecular with weak immunogenicity.

Highlights

Multi-field expert lead customized service.
First-in-class gene edition technique.
Target any identified antigens of tumors.
High-efficient discovery and fast delivery.

Interested in our Smart™ CAR construction services? Please send an email to contact us and let our experienced experts accelerate your subject.

Related Services

CAR Design and Construction. (Creative Biolabs)

CAR Design & Construction

Creative Biolabs offers classical CAR vectors design, first through fifth generation, and customized smart CAR design services.

FAQs

How does the NKG2D-based approach compare to established single-target CAR-T therapies, like anti-CD19?

Anti-CD19 CAR-T has been highly effective in specific hematological malignancies but is limited by single-antigen escape and minimal efficacy in solid tumors. Our NKG2D approach offers a pivotal advantage by targeting a family of ligands, inherently addressing tumor heterogeneity and minimizing the risk of antigen loss-driven relapse. It provides a robust, multi-pronged attack mechanism specifically designed for the complex landscape of solid tumors.

What is the primary precaution regarding potential off-target toxicity with NKG2D-CARs?

Because NKG2D ligands are stress-induced, their expression on healthy, non-stressed tissue is typically negligible, providing a high therapeutic index. However, non-malignant inflammation or tissue damage can temporarily upregulate ligands. Our approach includes rigorous multiplexed in vitro assays against a wide panel of healthy primary cell lines to confirm minimal off-target activity, allowing us to generate the safest possible construct for clinical translation.

Why Choose Us?

Creative Biolabs stands ready to accelerate your journey in immuno-oncology. Our NKG2D-based multi-target CAR construction service provides the critical solution required to defeat tumor heterogeneity, enhance safety, and unlock therapeutic efficacy in challenging solid tumors. By choosing our expert team, you gain access to proven scientific methodology, high-quality vectorology, and a strategic partner dedicated to translating your research into a clinical reality.

Reach out to our team today to discuss how the NKG2D platform can be specifically tailored to your proprietary tumor targets and clinical objectives.

Reference

Slavuljica, Irena et al. "Manipulation of NKG2D ligands by cytomegaloviruses: impact on innate and adaptive immune response." Frontiers in immunology. (2011) 2 85.

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.