Cytokine Release Syndrome (CRS)

CRS is one of the serious side effects of chimeric antigen receptor (CAR) T-cell therapy, with an incidence rate of 40-100% in patients receiving CAR-T therapy and can occasionally be fatal. Symptoms such as fever, fatigue, nausea, vomiting, diarrhoea and shortness of breath are commonly found.​

Key features of CAR-T induced CRS​

  • Activation of CAR-T via binding to its target antigen​

  • Over-activation of bystander immune cells resulting in release supraphysiological levels of pro-inflammatory cytokines such as IL-1, IL-6, IFN-γ, and GM-CSF.​

  • Myeloid / Monocyte derived IL-1 and IL-6 are required for CRS.​

How it is constructed

Deliverables​

  1. Body weight and mortality​

  2. Tumor growth kinetics​

  3. Cytokine profiling ​

  4. Immunophenotyping analysis​

  5. Histopathology​

Data

Myeloid-dominant HiMice supports the growth of Nalm-6, a CD19+ B-cell precursor leukemia cell line and acts as target cancer cells for CD19-CAR-T cells in CRS model.​

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and inteleukin-3 (IL-3) act as mediators of myelopoiesis in Myeloid-dominant HiMice, which help in generation and differentiation of myeloid cells for CRS investigation. ​

Tumor bearing mice injected with CD19-CAR-T cells exhibited increased body weight loss, increased mortality rate and elevated levels of pro-inflammatory cytokines within the first six days post treatment compared to mice injected with untransduced T cells.​

Given the complexity of human disease, in-depth knowledge of each model is key to success in pre-clinical studies. Invivocue offers tailor-made study designs to suit your research needs.​