KIR CAR Construction Services

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

KIR-based CAR design is a pioneering approach in the field of CAR-T therapy. It involves the incorporation of Killer-cell Immunoglobulin-like Receptors (KIRs) into the CAR construct. KIRs are a family of cell surface proteins found on natural killer (NK) cells and a subset of T cells. These receptors play a pivotal role in regulating the immune response by interacting with Human Leukocyte Antigens (HLAs) on the surface of target cells.

By integrating KIRs into CAR-T cells, our KIR-based CAR design service at Creative Biolabs aims to enhance the specificity, efficacy, and safety of CAR-T therapy. This innovative approach provides a means to fine-tune the immune response and overcome certain limitations of conventional CAR-T therapies, especially in the context of solid tumors and the challenges posed by the tumor microenvironment.

Figure 1 DAP12-based KIR CAR design. (Wang, et al. 2015) Fig.1 DAP12-based KIR CAR design.¹

KIR CAR Construction Services

Our expert team of scientists and engineers is proficient in designing, optimizing, and validating KIR-based CAR-T constructs. The key components of our KIR CAR construction services include:

KIR Selection and Optimization
We employ a rigorous process for the selection of KIRs based on their compatibility with the target tumor and their immunomodulatory properties. Through advanced bioinformatics and molecular modeling, we optimize the KIR component for maximal binding affinity and functionality.
KIR CAR Design and Construction
Our CAR vector design is characterized by precision and efficiency. We incorporate the KIR segment seamlessly into the CAR construct, ensuring proper co-expression with other CAR components. The design of the CAR vector is tailored to the specific requirements of the therapy.
KIR CAR Validation
Before advancing to clinical trials, our KIR CAR constructs undergo rigorous in vitro and in vivo validation. This step is critical to assess the functionality, safety, and efficacy of the KIR-based CAR-T cells.
Customization and Scale-Up
We understand that each therapeutic application is unique. Therefore, we offer customizable KIR CAR construction services, allowing for the fine-tuning of CAR-T cells to target different tumor types or to address specific patient needs. Our capabilities extend to scalable production for clinical trials and commercial applications.

Advantages of KIR CAR-T

A CAR constructed using this natural multi-chain immunoreceptor design offers several compelling reasons for showing sustained efficacy in CAR-T resistant tumor models, ultimately leading to complete tumor remission:

Prolongs T Cell Function: This design allows T cells to maintain their functionality over an extended period, ensuring a sustained immune response against the tumor.
Bypasses CD3ζ Co-Stimulation: The activation pathway in the DAP12 molecule enables T cells to activate without the need for CD3ζ co-stimulation. This unique feature enhances the CAR's effectiveness in the face of resistance.
Prevents T Cell Exhaustion: KIR-CAR T cells can be activated by coupling the receptor chains, and they can rest by decoupling them. This dynamic regulation helps prevent T cell exhaustion, ensuring their long-term activity against the tumor.
Stable Expression on T Cell Surfaces: KIR CARs express on both activated and non-activated T cell surfaces consistently. This stability signifies their superior anti-tumor function, especially in the challenging microenvironments of solid tumors.

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Reference

Wang, E.; et al. Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based Multichain Chimeric Immunoreceptors. Cancer Immunology Research. 2015, 3(7):815-826.