Neurotoxicity characterized after infusion of CD19 CAR-T cells

October 12, 2017

(HealthDay)—Patients with severe neurotoxicity after infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells have evidence of endothelial activation, according to a study published online Oct. 12 in Cancer Discovery.

Juliane Gust, M.D., Ph.D., from the University of Washington in Seattle, and colleagues characterized neurologic adverse events in 133 adults with refractory B-cell malignancies treated with lymphodepletion chemotherapy followed by infusion of CD19 CAR-T cells.

The researchers found that there were correlations for , high CD19+ cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and pre-existing neurologic comorbidities with elevated risk of neurologic adverse events. There was evidence of endothelial activation among patients with severe neurotoxicity, including disseminated intravascular coagulation, capillary leak, and elevated blood-brain barrier (BBB) permeability. The permeable BBB did not protect the cerebrospinal fluid from high concentrations of systemic cytokines, including interferonγ, which induced brain vascular pericyte stress and secretion of endothelium-activating cytokines. The brain of a patient with fatal neurotoxicity had endothelial activation and multifocal vascular disruption. In patients who subsequently developed grade ≥ 4 neurotoxicity, biomarkers of endothelial activation were higher before treatment.

"We show and increased BBB permeability in neurotoxicity and find that with evidence of endothelial activation before lymphodepletion may be at increased risk of ," the authors write.

Several authors disclosed financial ties to the biopharmaceutical industry, including Juno Therapeutics, which partially funded the study.

Explore further: Studies advance methods to avert toxicity that can accompany immunotherapy

More information: Abstract/Full Text (subscription or payment may be required)

Related Stories

Studies advance methods to avert toxicity that can accompany immunotherapy

October 12, 2017
Two new papers from researchers at Fred Hutchinson Cancer Research Center provide the most comprehensive data yet reported on side effects of the emerging cancer immunotherapy strategy known as CAR T-cell therapy.

Patient's immune status associated with outcome following third-generation CAR T-cell therapy

September 6, 2017
Treatment with third-generation CAR T–cell therapy led to a complete response in six of 15 patients with a CD19-positive B-cell malignancy and overall survival was associated with the patient's immune status, according ...

CAR T-cell therapy for leukemia leads to remissions in clinical trial

July 17, 2017
Researchers at Fred Hutchinson Cancer Research Center showed about 70 percent of patients with the most common adult leukemia had their tumors shrink or disappear following an experimental chimeric antigen receptor (CAR) ...

Ca2+, the intercellular signal in arterioles

July 4, 2017
Vasoconstriction must be balanced with vasodilation, particularly in the arterioles that supply tissues with blood. Endothelial cells protrude through holes in the internal elastic lamina in arterioles to make contact with ...

CD19-targeting CAR T-cell immunotherapy yields high responses in treatment-resistant CLL

December 3, 2016
In a small, early phase trial, a high percentage of patients who had exhausted most traditional treatments for chronic lymphocytic leukemia saw their tumors shrink or even disappear after an infusion of a highly targeted, ...

Study shows promising clinical activity

December 5, 2016
Immune cellular therapy is a promising new area of cancer treatment. Anti-cancer therapeutics, such as chimeric antigen receptor (CAR) modified T cells, can be engineered to target tumor-associated antigens to attack and ...

Recommended for you

Targeting telomeres to overcome therapy resistance in advanced melanoma

March 21, 2018
A study conducted at The Wistar Institute in collaboration with The University of Texas Southwestern Medical Center has demonstrated the efficacy of targeting aberrantly active telomerase to treat therapy-resistant melanoma. ...

A small, daily dose of Viagra may reduce colorectal cancer risk

March 19, 2018
A small, daily dose of Viagra significantly reduces colorectal cancer risk in an animal model that is genetically predetermined to have the third leading cause of cancer death, scientists report.

Cancer comes back all jacked up on stem cells

March 19, 2018
After a biopsy or surgery, doctors often get a molecular snapshot of a patient's tumor. This snapshot is important - knowing the genetics that cause a cancer can help match a patient with a genetically-targeted treatment. ...

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.