Interested in in vitro assays to assess the risk of cytokine storms? Or in vitro evaluation of compound effects on leukemic progenitors vs normal progenitors? So are we!
ReachBio Research Labs presented two posters at the recent Society of Toxicology conference in Phoenix, AZ. One on comparing assays for cytokine storm risk assessment of biologics and the other on an in vitro assay for evaluating the effects of compounds on leukemic progenitors vs their normal bone marrow counterparts. Please feel free to download a copy of each.
Click on the title to download a copy of the poster.
"Comparison of three methods for the evaluation of cytokine storm risk in early and clinical stage biopharmaceutical development"
Presenting author: Gary dos Santos
Abstract #270, Poster board #455
Monday, March 24
9:30am – 12:30pm
INTRODUCTION
Cytokine Release Syndrome and Cytokine Storm (CRS or CS) are potentially fatal immune reactions characterized by large-scale release, upon a first infusion of some therapeutic antibodies or biologics, of the proinflammatory cytokines IL2, IL4, IL6, IL8, IL17, TGFb, TNFa and/or IFNg by immune cells.
In 2006, a Phase I clinical trial of TGN1412, a humanized anti-CD28 superagonist, caused a near-fatal cytokine storm reaction in 6 out of 6 healthy volunteers. The adverse reaction to TGN1412 was not predicted by the standard battery of preclinical in vitro or in vivo tests, including NHP GLP studies. Subsequent analysis of interspecies differences found that the underlying cells responsible for the cytokine storm, CD4+CD4SRO+ effector-memory T cells, express CD28 in humans but not in primates. In addition, human lymphoid T cells, but not peripheral blood effector-memory T cells, were found to be reactive to TGN1412 raising questions about the utility of in vitro or ex vivo testing using PBMCs for CRS.
"An Ex vivo platform to evaluate the differential effects of potential therapies on leukemia progenitors (CFU-L) vs normal bone marrow progenitors (CFU-GM)"
Presenting author: Emer Clarke (CSO)
Abstract #1920, Poster board #321
Wednesday, March 26
1:00pm – 4:30pm
INTRODUCTION
Combination therapies are being increasingly employed to treat diseases where single agents do not have the desired clinical benefit. Acute myeloid leukemia (AML) is a malignant disease characterized by rapid growth of myeloid cells in BM. This year, 14,500 new cases will be diagnosed in the US, while claiming the lives of approximately 10,000. Nearly 40 years have passed since the development and implementation of cytarabine (Ara-C) and daunorubicin (DNR) combination therapy as a standard of care. However, in clinical trials additional drugs have been introduced as novel treatment regimes, either alone or in combination with standard treatments. A relevent ex vivo assay that reflects the potential of novel treatments may facilitate the discovery of more useful drug candidates. Flow cytometric and CFC assays provide ex vivo platforms in which the diversity of the disease parameters as well asthe utility of novel compounds can be tested. To this end we used eight color flow cytometric analysis to determine the cellular phenotypes of AML and NBM. Using the CFC assays, we evaluated the effects of drug combinations on NBM progenitors and AML CFU-L.
