CAR-T Toxicity and Safety
Creative Animodel offers comprehensive in vivo toxicity evaluation of CAR-T therapy. We use human tumor xenograft mouse or rat as models and provide you with detailed analysis before applying your CAR-T therapy into clinical trials.
Cytokine release analysis
CAR-T cell therapy has produced promising results in clinical trials, but its associated death incidents raised safety concerns. When the chimeric antigen receptor (CARs) recognizes its antigen, activated CAR-T cells will release cytokines, which supports CAR-T cells amplification and persistence during the therapy. However, sudden large amount of cytokines leads to cytokine storm syndrome that could cause high fever, illusion and even death. Cytokine storm is associated with CAR-T cell efficacy and tumor burden. Almost all patient who had tumor remission with CAR-T cell therapy experienced cytokine storm syndrome, and the larger the tumor, the more severe cytokine storm syndrome the patient will experience. To maximizing CAR-T cell potency and minimizing side effect, toxicity management is crucial for CAR-T cell therapy during cancer treatment.
Creative Animodel offers analysis of single or multiplex cytokine level analysis for your CAR-T cells using immunodeficient mouse or rat model with corresponding human tumor xenograft. Our scientists will assist you in assay development and data analysis to advance the process of your therapy into clinical application.
Cytokine release analysis:
✓ Time course and end point cytokine release analysis
✓ ELISA or cytokine array for multiplex cytokine release analysis
Normal cell aplasia
Since antigens expressed by B cell lymphoblast leukemia are also expressed on normal B cells, while B cell leukemia is treated, patient also experience normal B cell depletion and suffers from the results of weak self immune-response. Similar scenario could happen when CAR-T cells are targeting solid tumor cells, but part of normal tissue cells also expressing same antigens as the tumor. It is therefore important to assess of noncancerous cell deaths caused by CAR-T cells for safety assessment before applying the treatment in patients. Aside from proper design and selection of tumor antigens during CAR-T engineering, it is important to analyze these potential side effects during preclinical studies. Creative Animodel offers comprehensive cell content analysis for assessment of non-tumor cell targeting of CAR-T therapy.
✓ Hematopoietic cell content analysis
✓ Animal necropsy and histological analysis
Tumor lytic syndrome
CAR-T cells recognize tumor cells and kill them through apoptosis, but studies have revealed that certain amount of tumor cells targeted by lymphocytes could also die through necrosis. Necrotic cells release toxic products from cell death, causing inflammation and damage to the surrounding healthy cells. This side effect raises safety concerns during CAR-T cell therapy. Proper control of tumor cell necrosis is crucial for providing the safe therapy for the patients. Creative Animodel offers analysis of tumor cell lysis during CAR-T cell treatment in tumor xenograft mouse or rat model for it toxicity and safety assessment.
Tumor lysis analysis includes:
✓ Chrinium release cytotoxicity assay
✓ Potassium Phosphate levels analysis
✓ Serum uric acid level analysis