Cytokine Release Syndrome (CRS) Studies

A rapid, reproducible, and highly flexible platform to more accurately evaluate the systemic implications of cytokine release associated with novel human-targeted-specific immunomodulatory drugs. It can be used to quickly and accurately select leads based on efficacy as well as toxicity caused by cytokine release.

CRS Evaluation studies can provide valuable information for:

Lead Selection
Compare different lead candidates.

Efficacy
Optimize dose range for tumor shrinkage or removal of target.

Safety
Determine which molecule/dosage provides minimal toxicity by using one PBMC donor for the study.

Preclinical Variability
Test the optimal dosages against the diversity of the population by using multiple PBMC donors in the study.

What is Cytokine Release Syndrome?
How is CRS used for Bispecific Antibody Development?
What to Expect for a JAX CRS Evaluation Study

What is Cytokine Release Syndrome?

Cytokines are a part of the innate immune system. A number of factors can cause cytokines to be triggered, but when a mass release of cytokines occurs, iti s known as a cytokine storm. Cytokine storm creates a toxic environment that in extreme situations can be lethal.

For information about what cytokine release syndrome has to do with drug development, watch the "What is CRS?" video.

Sample CRS Study

Models

NSG
000557

013062

NSG-MHC class I/II DKO
002516

Adult PBMC (5 to 20x106) from single or multiple donors

Groups

4-5 Mice/arm; 6-10 days/study

Data

  • Panels of Compounds Tested
  • CRS in relationship to compound efficacy
  • Sera collection for cytokines (1 to 6 hrs post dose)
  • Animal clinical evaluation (CRS score, body weight)
  • Body temperature
  • Immunophenotyping
  • Downstream toxicity to the humanized mouse
    (e.g. liver function, histology)
Sample CRS Study - Understanding Population Diversity with Multiple PBMC Donors

CRS Evaluation StudY Online Resources