What are CAR-T cells?

CAR T cells, or chimeric antigen receptor T cells, are a type of genetically engineered immune cell that targets cancer cells in a patient's body. They are modified T cells extracted from a patient's blood and reprogrammed with CAR molecules that allow them to recognize and attack cancer cells. Once infused back into the patient, the CAR-T cells multiply and actively seek out and destroy cancer cells.

What is a chimeric antigen receptor?

A chimeric antigen receptor (CAR) is a receptor protein artificially engineered to attach to the surface of immune cells . It consists of an extracellular domain that binds to specific antigens on cancer cells, and an intracellular domain that activates the immune cell to kill the targeted cancer cell. CARs are engineered in the laboratory and can be used in immunotherapy to treat cancer by enhancing the immune system's ability to destroy cancer cells.

How are CAR-T cells made?

CAR T cells are made by collecting T cells from a patient's blood and genetically engineering them to express a chimeric antigen receptor (CAR) that recognizes and binds to a specific antigen on the cancer cell's surface. The engineered CAR-T cells are expanded in the lab and then infused back into the patient. Once inside, the CAR-T cells locate and bind to cancer cells, triggering an immune response that destroys the cancer cells.

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Background Services Highlights Resources Related Sections

A new era of cancer immunotherapy has begun. Chimeric antigen receptor T (CAR-T) cells, which have been genetically engineered to recognize the CD-19 antigen of B cells, have been successfully treated in various clinical trials for relapsed and refractory B cell malignancies. However, this treatment has several disadvantages. Side effects such as cytokine toxicity, tumor lysis syndrome, effects on healthy tissues, B cell hypoplasia, and genotoxicity can be fatal.

To avoid these drawbacks, CAR technology is being applied to other immune cells, such as natural killer (NK) cells. Unlike T cells, NK cells can be more easily fine-tuned to prevent treatment-related toxicity and immune-mediated adverse events. NK cells have great clinical significance because they contribute to graft-vs-leukemia / graft-vs-tumor effect but are not responsible for graft-vs-host disease. NK cells can be generated from various sources, such as cord blood, bone marrow, human embryonic stem cells, and induced pluripotent stem cells.

Primary NK cells engineered to express CAR have potential advantages over CAR-T cells.

NK cells have spontaneous cytotoxic activity and can cause target cell death independent of tumor antigens, while T lymphocytes only kill their targets through CAR specific mechanisms. Therefore, NK cells will still be effective against tumor cells in the case of down-regulation of tumor cells that are trying to evade immune detection.
Primary human NK cells produce cytokines such as interferon gamma, interleukin 3, and granulocyte macrophage colony stimulating factor, which are different from the proinflammatory cytokines produced by T cells responsible for the onset of cytokine release syndrome.
A single NK cell can survive after contacting and killing multiple target cells, which may reduce the number of cells that require adoptive transfer, as opposed to T cells.
In addition, although the long-term persistence of CAR-T cells can maintain on-target and off-tumor toxicity, mature NK cells have a short lifespan and are expected to disappear after promoting their anti-cancer effects.

Therefore, NK cell lines are attractive for CAR cell therapy.

CAR-NK Therapy Development Solutions

As the leading cell therapeutics biotech that provides cell therapy related services, Creative Biolabs masters the most advanced CAR technology. With state-of-art CAR development platforms and advanced technologies, Creative Biolabs is capable of offering a broad range of CAR-NK early development services, including CAR engineered T cell biomarker identification and selection, design, construction, and analysis.

Biomarker Identification & Selection High Affinity ScFv Generation CAR-NK Vector Design and Construction Virus Packaging & CAR Gene Delivery CAR-NK In Vitro Assay CAR-NK Preclinical In Vivo Assay CAR-T Clinical Trial

De novo discovery of potential cancer biomarkers by multiple gene and protein analysis technologies
Selection of the most suitable CAR-NK therapy targets with greater potency and lower toxicity

In-house inescapable antibody sequence data base
A collection of over 6000 antibody products
Antibody discovery by hybridomas, mouse, rabbit and human library
ScFv sequencing and NGS of hybridomas or phage libary
ScFv affinity measurement and optimization

Design and construction of CARs of different generation
Smart™ CAR platform for the next generation CAR discovery
Customized lentiviral or retroviral CAR construction

High titer transduction-ready pseudoviral particles produced by our cell manufacture platform
Strict quality control
Various transfection technology available
Transfection method tailored for different cell types

CAR expression validation
CAR-NK cell proliferation
Multiplex cytokine screening
Cytotoxicity test against target cells

Construction of Xenograft Animal Model
Efficacy Test of CAR-NK cells
Viability and Bio-distribution Study of CAR-NK cells
Toxicity Evaluation of CAR-NK cells
GLP-compliant assays

Study design and filing
Project management and execution
Data management and biostatistics
QA&QC

Creative Biolabs has also developed a series of novel platforms for enhanced CAR-NK Therapy. Please visit:

Highlights & Advantages

Enhanced Safety Profile
CAR-NK cells are engineered to minimize treatment-related toxicities, including cytokine release syndrome and graft-vs-host disease, offering a safer alternative to CAR-T cell therapies.
Superior Cytotoxic Activity
Unlike T cells, NK cells exhibit spontaneous cytotoxic activity and can kill target cells independent of tumor antigens, making them effective even against tumor cells that down-regulate antigens to evade immune detection.
Cytokine Production
Primary human NK cells produce beneficial cytokines like interferon gamma and interleukin 3, which support anti-tumor activity without causing the severe inflammatory responses associated with CAR-T cells.
Efficient Target Cell Killing
A single NK cell can engage and kill multiple target cells, potentially reducing the number of cells needed for adoptive transfer and improving treatment efficiency.
Short Lifespan for Reduced Toxicity
Mature NK cells have a shorter lifespan than CAR-T cells, reducing the risk of prolonged on-target/off-tumor toxicity after treatment, as they are expected to disappear after exerting their anti-cancer effects.
Diverse Cell Sources
NK cells can be generated from various sources, including cord blood, bone marrow, human embryonic stem cells, and induced pluripotent stem cells, providing flexibility in therapy development.
Expertise in Genetic Engineering
Provides comprehensive NK cell genetic engineering services, including NK cell expansion and the development of iPSC-derived CAR-NK therapies, enhancing the versatility and applicability of CAR-NK cell therapies.
Regulatory and Clinical Support
Expert support in study design, project management, data management, biostatistics, and QA&QC for seamless transition from preclinical development to clinical trials.
Customization and Flexibility
Tailored solutions for different cell types and specific research requirements, ensuring the development of highly effective and personalized CAR-NK therapies.

Resources

Use the resources in our library to help you understand your options and make critical decisions for your study.

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Natural Killer Cell Based Therapeutics

CAR Design & Construction Service

Overview of Chimeric Antigen Receptors

Chimeric antigen receptor (CAR) can combine the extracellular antigen recognition domain from antibodies with the immune cell signaling domain to redirect T cell specificity and induce potent antitumor activity. CAR is an artificial transmembrane receptor that connects the extracellular antigen recognition domain, hinge domain (HD), transmembrane domain (TMD), and intracellular signal transduction domain in series.

NK Cell-based Immunotherapy

Natural killer (NK) cells are vital components of the innate immune system, playing a crucial role in fighting viral infections and preventing cancer. Comprising 10%-15% of human peripheral blood lymphocytes, NK cells are distinguished by their cytolytic granules, which release perforin and granzymes to induce apoptosis in abnormal cells. They also produce cytokines like IFN-γ, TNFα, and GM-CSF to activate and recruit other immune cells. NK cells are classified into CD56dim (highly cytotoxic) and CD56bright (cytokine-producing) subsets based on surface markers. Their immune responses are controlled by a balance of activating and inhibitory receptors. NK cells are targeted in various immunotherapies, including monoclonal antibodies, adoptive NK cell therapy, CAR-based NK cell immunotherapy, NK cell-targeted vaccines, and therapies targeting cancer stem cells (CSCs). These therapies leverage NK cells' ability to kill tumor cells and form memory cells, offering promising strategies for cancer and disease treatment.

Adoptive NK Cell Therapy

Cancer immunotherapy, which activates the immune system, has become crucial in cancer treatment. NK cells, innate immune cells, are key in immune surveillance, killing abnormal cells and cancer stem cells without prior sensitization. They release cytolytic granules to induce cell lysis and have been used in adoptive transfer to target tumors, especially hematological malignancies. However, tumor cells evade NK cell-mediated immunity through various strategies, such as altering NK cell receptors and creating an immunosuppressive tumor microenvironment (TME). NK cells regulate their responses to avoid harming healthy tissues by inhibiting receptors like KIR, NKG2A/CD94, and LILR. They destroy tumor cells via receptor-mediated cytotoxicity, ADCC, and death receptor-mediated apoptosis, and enhance adaptive immune responses through cytokine production. Tumor cells counteract these mechanisms by downregulating activating ligands and secreting immunosuppressive factors. Adoptive transfer of autologous, allogeneic, and stem cell-derived NK cells, as well as NK cell lines and memory-like NK cells, shows promise in overcoming these challenges and improving anti-tumor responses in immunotherapy.