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, it is 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.

CRS and Bispecific Antibody Development

Bispecific antibodies are shown to be a promising approach to cancer immunotherapy, but CRS is a known issue when developing these therapeutics. The CRS Evaluation Studies can evaluate Bispecific T-cell Engagers (BiTEs) alone, or in combination with other therapeutics.

When evaluating bispecific drugs, it is important for a tumor antigen to be present in the model. The bispecific reaching to the tumor antigen is what triggers the cytokine release response. JAX has access to a large library of PDX Tumors that can be engrafted into the NSG models utilized in the CRS Evaluation Studies, giving researchers access to optimal tumor models and optimal translationally relevant environments.

Bispecific antibodies are shown to be a promising approach to cancer immunotherapy, but CRS is a known issue when developing these therapeutics. The CRS Evaluation Studies can evaluate Bispecific T-cell Engagers (BiTEs) alone, or in combination with other therapeutics.

When evaluating bispecific drugs, it is important for a tumor antigen to be present in the model. The bispecific reaching to the tumor antigen is what triggers the cytokine release response. JAX has access to a large library of PDX Tumors that can be engrafted into the NSG models utilized in the CRS Evaluation Studies, giving researchers access to optimal tumor models and optimal translationally relevant environments.

Bispecific antibodies are shown to be a promising approach to cancer immunotherapy, but CRS is a known issue when developing these therapeutics. The CRS Evaluation Studies can evaluate Bispecific T-cell Engagers (BiTEs) alone, or in combination with other therapeutics.

When evaluating bispecific drugs, it is important for a tumor antigen to be present in the model. The bispecific reaching to the tumor antigen is what triggers the cytokine release response. JAX has access to a large library of PDX Tumors that can be engrafted into the NSG models utilized in the CRS Evaluation Studies, giving researchers access to optimal tumor models and optimal translationally relevant environments.

Understand Population Diversity with Multiple PBMC Donors

By utilizing multiple PBMC donors, data can be gathered that predicts the therapeutic response amongst a generally diverse population.

Test for minimal toxicity but best tumor shrinkage against the diversity of the population by using multiple PBMC donors.

By utilizing multiple PBMC donors, data can be gathered that predicts the therapeutic response amongst a generally diverse population.

Test for minimal toxicity but best tumor shrinkage against the diversity of the population by using multiple PBMC donors.

Sample CRS Study

Models

NSG
005557

NSG-SGM3
013062

NNSG-MHC class I/II DKO
025216

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