CytoSorbents Corporation (CTSO)

[techxen]

New insights into CAR T-cell therapy
Detailed study of cytokine release syndrome and neurologic toxicities could help make emerging cancer immunotherapies safer.
https://www.fredhutch.org/en/news/center-news/2017/10/car-t-cell-side-effects-study.html

Obviously CRS is a major problem that Juno, Novartis, etc. have to solve even if it only effects 10% or less of patients (most severe). There were several points of interest from the Hutchinson findings:

1 - "One of the studies’ novel findings is that severe cases of both types of toxicities were associated with signs that endothelial cells — those lining blood vessels — were ramping up activity in response to injury." There was a Cytosorb case study in 2017 that they specifically noted the impact of cytokine removal on the vascular barrier breakdown on the endothelial surface. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251288/

2. "Using that information, they developed a two-part method to identify the patients who would go on to develop severe CRS. Within the first day and a half after T-cell infusion, the red flags were a fever of at least 102 degrees Fahrenheit and high levels of one particular immune-signaling chemical, a cytokine known as MCP-1. The algorithm was relevant to all three cancer types included in the trial.". The use of Cytosorb in numerous cases have resulted in a decrease of both pro- and anti-inflammatory cytokines during and after each session, especially for IL-6, IL-10 and MCP-1. Here is one: http://cytosorb-therapy.com/case-report/first-use-hemoadsorption-device-cytosorb-continous-venovenous-hemofiltration-cvvh-patient-undergoing-retransplantation-abo-incompatible-graft-acute-graft-dysfunctio/

3. "While an effective therapy for CRS is FDA-approved — a cytokine-modulating drug and/or a steroid — it is unclear what the best protocol is for early intervention in the development of side effects. The data from their study could inform the design of a clinical trial to test the best strategy for blunting the development of the most serious cases, the researchers say.". I am assuming the drug they are referring to is tocilizumab, which Dr. Chan stated that this is not always effective.

The Hutchinson article did not mention the related disorder of HLH, of which Cytosorb has been used successfully to treat 10 patients with 3 published case reports. From this Cytosorbents press release it seems that the company's data they have gathered on these case studies is what will open the door possibly for using it to treat specifically CRS: http://cytosorbents.com/cytosorb-treatment-of-hlh-the-parallel-to-cytokine-release-syndrome-in-cancer-immunotherapy/

Lastly, it seems that since Juno is funding this work at Hutchinson they may be trying to leap frog others to solving the CRS problem. I would assume Novartis/University of Pennsylvania and Dr. June are also working towards this as well and leveraging these findings.