Creative Animodel provides comprehensive analysis of CAR-T cells pharmacokinetics in xenograft animal models. Our services will provide with valuable information for clinical outcomes predictions and toxicity evaluations
Circulating CAR-T cells needs to meet their target cancerous cells before killing them through apoptosis. It is easier for CAR-T cells to target blood cancer cells as hematopoietic cells are mostly circulating in the blood stream. However, it could be challenging for CAR-T cells to target solid tumors cells as most of solid tumors tend to build up their “walls” to protect themselves against immune cell targeting. Failure to find the location of the tumor could leads to failed treatment and even severe side effects. CAR-T cell may infiltrate into other noncancerous tissues that happen to express its targeting antigen and result in off-targeting of normal cells and possible organ failure. It is therefore important to monitor the distribution of CAR-T cells after its administration. Creative Animodel offers preclinical studies of CAR-T distribution in human tumor xenograft mouse or rat models for both safety and efficacy evaluation of your CAR-T cell therapy.
Methods used for biodistribution analysis:
✓ Animal necropsy and Immunohistochemistry of organ tissues for CAR-T cell infiltration
✓ Bioluminescence imaging of luciferase expressing CAR-T cells
The duration of CAR-T cells in the blood stream plays an important role in CAR-T efficacy. The longer CAR-T cells stay circulating in the serum, the longer the efficacy period will be for each dose of treatment. In some clinical studies, autologous CAR-T cells could be cleared out of the blood stream by host immune system before they could even have a chance to meet their targets. Therefore, it will be useful to assess the serum persistence of CAR-T cells for predict their clinical outcomes before applying the therapy in patients. Creative Animodel offers in vivo analysis of CAR-T serum persistence in human tumor xenograft mouse or rat models. This analysis provides valuable information for determining therapeutic dosage and predicting CAR-T efficacy in clinical trials.
The methods for serum persistence analysis:
✓ Establishing customized humanized xenograft mice or rats model.
✓ Flow cytometry analysis of hematopoietic cell contents
o Peripheral blood for circulating CAR-T cells
o Bone marrow for engrafted CAR-T cells
✓ PCR genotyping of CAR-T cells in peripheral blood samples and bone marrow
Figure 1. Humanized xenograft mouse model
We provide both time course analysis and end point assessment on serum persistence and biodistribution of CAR-T cells. With our experienced scientific team and state-of-the-art technology, we will advance the process of your CAR-T therapy into clinical trials.