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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CAR-T Toxicity Evaluation Service

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

Background Services Highlights Related Sections

CAR-T therapies have demonstrated great efficacy in hematologic malignancies and some solid tumors in early phase clinical trials. However, CAR-T cells may elicit some expected and unexpected toxicities such as cytokine release syndrome, tumor lysis syndrome, neurologic toxicity, on-target/off-tumor recognition, and anaphylaxis. In addition, theoretical toxicities such as insertional oncogenesis, graft versus host disease, and off-target/off-tumor antigen recognition, may be related to CAR-T cell therapy as well. Safety risk is the main concern in the development of new drugs and therapeutic novelties. Evaluation of the toxicity on animal models is essential to assure the safety and right of subjects. With extensive experience on preclinical in vivo research and project management, Creative Biolabs provides CAR-T cell toxicity evaluation service, by utilizing appropriate models, designing comprehensive research practices and handling high-quality in vivo studies.

Toxicity Evaluation of CAR-T

Toxicities of CAR-T therapy.
C Bonifant et al. 2016

Toxicity Evaluation Services

We provide the following toxicological study services on CAR-T cell therapy.

Clinical Observation
The safety of CAR-T cell therapy is evaluated by standard toxicological studies. Body weight, feed consumption, behavior, morphology, ophthalmologic and pathologic characteristics are closely monitored. After specific end point, a complete necropsy including assessment of organ weight and histopathology analysis is conducted.

Cytokine Release Analysis
To date, the most prevalent side effect of CAR-T cell therapy is the onset of immune activation, also known as cytokine release syndrome (CRS). Cytokines can support the amplification and persistence of CAR-T cells in vivo. On the other hand, sudden elevation of cytokine levels usually leads to high fever, fatigue, hypotension, and nausea, which can further result in life threatening reactions. Therefore, the cytokine level information in animal models is of great value for risk management of CAR-T cell therapy. Creative Biolabs offers multiplex cytokine release analysis with ELISA or cytokine array for evaluating your CAR-T cells. Both time course and end point cytokine release analysis will be conducted.

Tumor Lysis Analysis
CAR-T cells bind the cognate antigen on the target tumor cells and kill them. The rapid destruction of large amount of tumor cells lead to tumor lysis syndrome due to the abrupt release of cellular toxic products, causing a set of systemic metabolic disturbances. This side effect elicits safety concerns of CAR-T cell therapy. Creative Biolabs offers tumor lysis analysis during CAR-T cell evaluation in animal models for toxicity and safety assessment. The analysis mainly contains chromium release cytotoxicity assay, potassium phosphate levels analysis and serum uric acid level analysis.

On-target/off-tumor Toxicologic Effect Analysis
In most cases, the target of CAR may not be specific for tumor cells and expresses in healthy tissues at low levels as well. Therefore, CAR-T cells may target these normal cells and results in adverse reactions ranging from manageable and acceptable lineage depletion (B cell aplasia) to severe toxicity that may cause death. Creative Biolabs provides on-target/off-tumor toxicologic effect analysis that mainly contains cell content analysis, animal necropsy and histological analysis.

Tumorigenicity Study
Tumorigenicity study is performed in immunocompromised animals to assess the potential of ectopic tissue formation or cell phenotypic stability of CAR-T cells. The engineered T cells are administrated with at least three dose groups (including positive control). Animals are palpated for mass presence weekly and tissues are preserved for histologic and cell detection. The study typically lasts the whole lifespan of the animals.

Other toxicities, such as neurologic toxicity, anaphylaxis, graft versus host disease, and off-target/off-tumor antigen recognition will also be closely monitored during the study.

All of the studies are conducted in a GLP-compliant and IACUC-regulated facility. We are pleased to share our precious experience on CAR-T cell toxicity evaluation with our clients. Our experienced experts will help you design the program that best meet your purpose and expedite your CAR-T cell therapy to clinical trials.

Highlights & Advantages

Comprehensive Toxicity Testing
Our services cover a wide range of potential toxicities associated with CAR-T therapies, including cytokine release syndrome, tumor lysis syndrome, neurologic toxicity, and off-target effects, among others.
Advanced Analytical Methods
Utilization of sophisticated analytical techniques such as multiplex cytokine assays, cytotoxicity assays, and comprehensive metabolic analyses to provide detailed insights into the safety profile of CAR-T cells.
Innovative Technologies
Integration of the latest technological advancements in toxicology and immunotherapy to provide state-of-the-art evaluation services that keep pace with the rapidly evolving field of CAR-T therapy.
High-Quality Animal Models
Employing the most appropriate and validated animal models for toxicity studies, ensuring reliable and translatable results that reflect human responses.
Risk Mitigation
Proactive identification and management of potential risks associated with CAR-T therapies, aiding in the development of safer and more effective treatments.
Regulatory Compliance
All studies are conducted in compliance with GLP (Good Laboratory Practice) and IACUC (Institutional Animal Care and Use Committee) regulations, ensuring ethical standards and data integrity.
Customized Evaluation Plans
Tailored toxicity evaluation plans designed to meet the specific needs of each client, ensuring precise and relevant data for regulatory submissions and clinical development.
Data-Driven Insights
Providing comprehensive and data-driven insights that inform decision-making and enhance the development of CAR-T cell therapies, ensuring a robust safety profile.
Accelerated Development Timelines
Streamlined processes and efficient project management help expedite the completion of toxicity evaluations, accelerating the overall development timeline for CAR-T therapies.
Extensive Expertise
Creative Biolabs leverages years of experience and cutting-edge technology to provide unparalleled CAR-T cell toxicity evaluation services, ensuring the highest standards of safety and efficacy.
Experienced Scientific Team
Our team of experts, with extensive backgrounds in immunology and oncology, provides expert guidance throughout the toxicity evaluation process, from study design to data interpretation.
Collaborative Approach
Close collaboration with clients to understand their specific requirements and provide tailored solutions that support their research and development goals.