Engineered Chimeric Antigen Receptor T (CAR-T) cell is the leading immune-therapy in oncology. Clinical trials have produced encouraging results in CAR-T involved cancer treatments. Despite of the positive results from the clinics, CAR-T therapy associated safety issues still pose risks in its clinical applications. Preclinical assessment of CAR-T efficacy and safety are necessary for its dosage determination and risk managements.
Creative Animodel provides customized preclinical testing services for your CAR-T cells. In cooperation with our CAR-T cells production division, Creative Biolabs, we are able to provide you with one-stop full service of both CAR-T production and preclinical testing. We also offer services for customized CAR-T cell toxicity management assessments.
We conduct CAR-T cell preclinical studies in human tumor sample derived xenograft mouse/rat models. Immunodeficient mouse/rat that lack functional B cells, T cells, or NK cells, and with reduced innate immunity are the optimal animal models for engraftment of human tumor cells. In addition, these immunodeficient small animals also support engraftments of modified human immune system, including CAR-T cells, for better clinical modeling.
CAR-T preclinical studies in human tumor xenograft mouse/rat model
Our preclinical study services includes:
✓ Establishing of xenograft mouse/rat model
✓ Cytotoxicity assay to determine Effector: Target ratio
✓ CAR-T biodistribution and serum persistence
✓ Evaluation of CAR-T efficacy
✓ Assessment of CAR-T associated toxicity
✓ Customized toxicity management
General flow scheme of CAR-T preclinical study services
1. Establish tumor xenograft mouse/rat models based on client's purpose of study and assessment of successful engraftments
2. CAR-T administration, sample collection and measurements for tumor targeting efficacy and CAR-T induced toxicity. Technology used includes, but not limited to, flow cytometry analysis, immunohistochemistry, cytokine panel analysis, etc.
3. Animal necropsy for end-point evaluation of CAR-T cell therapy efficacy
Services for CAR-T Pharmacokinetic studies:
✓ CAR-T serum persistence and engraftment
✓ CAR-T bidistribution and tissue infiltration
Services for CAR-T efficacy studies:
✓ Tumor cell measurements:
o Size measurements for solid tumor, body weight
o Tumor cell counts and flow cytometry analysis of peripheral blood and bone marrow for hematopoietic tumor
✓ End point animal necropsy for tissue weighing
✓ Tumor size monitoring by bioluminescent imaging
Services for CAR-T toxicity and safety evaluation:
✓ Cytokine panel analysis (end point or time course)
✓ Blood cell and bone marrow content monitoring by flow cytometry
✓ Cytotoxicity analysis for determine effector: target ratio and cell necrotic risk assessments
Our experienced scientists will help you to develop the study proposal that best suit your purpose and fast advance your drug through clinical trials.