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Chemokine Receptor engineered NK Cell Development Service for Chemotaxis Enhancement

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Are you currently facing challenges with limited NK cell trafficking to tumor sites, hindering the efficacy of your adoptive cell therapy projects? Creative Biolabs' chemokine receptor engineered NK cell development service helps you significantly enhance NK cell chemotaxis and improve tumor infiltration through advanced chemokine receptor engineering and cutting-edge gene modification techniques, accelerating your immunotherapy development.

Need for Enhanced NK Homing

The promise of gene therapy, particularly adoptive cell therapies utilizing Natural Killer (NK) cells, is immense for cancer treatment. However, a critical hurdle, especially for solid tumors, is the poor trafficking and infiltration of these therapeutic cells into the tumor microenvironment. Current research highlights that while NK cells possess potent anti-tumor capabilities, their ability to efficiently migrate to and persist within tumor sites is often limited by the lack of appropriate chemokine receptor expression. Enhancing NK cell chemotaxis through targeted chemokine receptor engineering is therefore paramount to unlocking their full therapeutic potential, ensuring these vital immune cells reach their intended targets effectively.

Fig.1 NK cells modified with chemokine receptors achieve increased tumor-directed. (OA Literature)Fig.1 NK cells engineered with chemokine receptors achieve enhanced tumor-directed.1

Chemokine Receptor engineered NK Cell Development Service for Chemotaxis Enhancement at Creative Biolabs

Creative Biolabs' chemokine receptor engineered NK cell development service provides a comprehensive solution for enhancing the migratory capabilities of your NK cells, leading to improved therapeutic outcomes. We achieve this by meticulously engineering NK cells with specific chemokine receptors through a streamlined multi-step process, typically completed within 10-16 weeks depending on project complexity. Our commitment to quality ensures we deliver highly characterized, functionally superior NK cell populations engineered for specific tumor homing, backed by rigorous validation and quality control.

Workflow: Streamlined Development for Enhanced NK Cell Therapies

Step 1

Project Consultation & Experimental Design

Our expert team will engage in a thorough discussion of your project objectives, target disease, and specific requirements. We will assist in selecting the most appropriate chemokine receptors (e.g., CXCR4, CCR5, CXCR2) based on your target chemokine profile and design a tailored engineering strategy.

Step 2

Gene Vector Construction & Optimization

We design and construct high-titer, safe, and efficient gene delivery vectors (e.g., lentiviral or retroviral vectors) encoding the chosen chemokine receptor(s). These vectors are optimized for robust and stable expression in NK cells.

Step 3

NK Cell Isolation & Expansion

NK cells are isolated from your provided source material using advanced isolation techniques to ensure high purity. These isolated NK cells are then expanded ex vivo using proprietary protocols to achieve sufficient cell numbers while maintaining their viability and functionality.

Step 4

Gene Transduction & Engineering

The expanded NK cells are transduced with the engineered gene vectors to introduce and express the desired chemokine receptor(s) on their surface. Our optimized protocols ensure high transduction efficiency with minimal impact on cell viability.

Step 5

Functional Validation & Characterization

Comprehensivein vitro assays are performed to validate the successful expression of the engineered chemokine receptors (e.g., flow cytometry). Crucially, the enhanced chemotactic function of the engineered NK cells towards target chemokines is rigorously assessed using migration assays. We also evaluate their in vitro cytotoxicity against target tumor cells.

Step 6

Quality Control & Final Deliverables

Rigorous quality control checks are performed on the final engineered NK cell product, including sterility testing, mycoplasma detection, and viability assessment.

Our Service Highlights

  • Enhanced Tumor Homing: Significantly improves NK cell migration to target tumor sites.
  • Increased Therapeutic Efficacy: Boost the anti-tumor activity of NK cell therapies.
  • Customizable Solutions: Tailored chemokine receptor selection and engineering strategies.
  • Robust & Reproducible: High-quality, validated engineered NK cells for reliable results.
  • Accelerated Development: Streamlined workflow to expedite your research timelines.

Case Study

In this study, two chemokine receptors, CCR4 and CCR2B, which are naturally found on T regulatory cells and tumor-resident monocytes, respectively, were overexpressed on NK cells. Using the NK cell line, as well as primary NK cells from peripheral blood, it was shown that genetically engineered NK cells can be efficiently redirected using chemokine receptors from different immune cell lineages and migrate towards chemokines such as CCL22 or CCL2, without impairing their natural effector functions.

Fig.2 CCR4- and CCR2B-transduced NK-92 cells migrate towards CCL22 and CCL2. (OA Literature)Fig.2 Transduced NK cell line with CCR4 and CCR2B move in the direction of CCL22 and CCL2.1

FAQs

Q1: What types of chemokine receptors can be engineered onto NK cells?

A1: We offer engineering for a wide range of chemokine receptors, including but not limited to CXCR4, CCR5, and CXCR2, which are commonly associated with tumor homing. Our service is highly customizable, and we can explore other receptors based on your specific research needs and target chemokine profiles.

Q2: How does engineering chemokine receptors enhance NK cell function in solid tumors?

A2: Solid tumors often create an immunosuppressive microenvironment that limits immune cell infiltration. By engineering NK cells with specific chemokine receptors, we equip them with the "GPS" to navigate towards chemokines highly expressed by tumor cells or within the tumor microenvironment. This targeted migration significantly improves their ability to reach, infiltrate, and exert their cytotoxic effects within the tumor, overcoming a major barrier to effective solid tumor immunotherapy.

Q3: Is it possible to combine chemokine receptor engineering with other NK cell modifications, such as CAR expression?

A3: Absolutely! Our platform is highly flexible. We can integrate chemokine receptor engineering with other modifications, such as Chimeric Antigen Receptor (CAR) expression, to create multi-functional NK cells. This combined approach can provide both enhanced tumor targeting (via CAR) and improved tumor homing (via chemokine receptors), leading to a more potent and effective therapeutic agent.

Related Services

Additionally, Creative Biolabs provides a range of well-established services to assist you design your NK cells for better functionalities:

Work with Creative Biolabs

As a reliable collaborator in the advancement of immunotherapy, Creative Biolabs provides a full range of chemokine receptor-engineered NK cell production services that are intended to boost the effectiveness of your cell therapies. If you have any further questions about our services, please don't hesitate to contact us.

Reference

  1. Feigl, Frederik Fabian et al. "Efficient Redirection of NK Cells by Genetic Modification with Chemokine Receptors CCR4 and CCR2B." International journal of molecular sciences vol. 24,4 3129. 4 Feb. 2023, doi:10.3390/ijms24043129. Distributed under Open Access License CC BY 4.0, without modification.
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