European Union’s Horizon 2020

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imSAVAR - Immune safety avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies

The vision of Immune Safety Avatar (imSAVAR) is to develop a platform for integrated nonclinical assessments of immunomodulatory therapy safety and efficacy.The imSAVAR is an Innovative Medicines Initiative funded project that aims to develop a standard for integrated nonclinical safety overviews for immune-modulatory investigational new drugs (IND) and clinical trial applications (CTA).Our imSAVAR platform will improve the prediction of the transferability of safety and efficacy of immunomodulators ...

Programme: European Union’s Horizon 2020

Public web page: https://imsavar.eu/

Transcriptional states of CAR-T infusion relate to neurotoxicity - lessons from high-resolution single-cell SOM expression portraying.
imSAVAR - Immune safety avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies

Abstract (Expand)

Anti-CD19 CAR-T cell immunotherapy is a hopeful treatment option for patients with B cell lymphomas, however it copes with partly severe adverse effects like neurotoxicity. Single-cell resolved molecular … data sets in combination with clinical parametrization allow for comprehensive characterization of cellular subpopulations, their transcriptomic states, and their relation to the adverse effects. We here present a re-analysis of single-cell RNA sequencing data of 24 patients comprising more than 130,000 cells with focus on cellular states and their association to immune cell related neurotoxicity. For this, we developed a single-cell data portraying workflow to disentangle the transcriptional state space with single-cell resolution and its analysis in terms of modularly-composed cellular programs. We demonstrated capabilities of single-cell data portraying to disentangle transcriptional states using intuitive visualization, functional mining, molecular cell stratification, and variability analyses. Our analysis revealed that the T cell composition of the patient's infusion product as well as the spectrum of their transcriptional states of cells derived from patients with low ICANS grade do not markedly differ from those of cells from high ICANS patients, while the relative abundancies, particularly that of cycling cells, of LAG3-mediated exhaustion and of CAR positive cells, vary. Our study provides molecular details of the transcriptomic landscape with possible impact to overcome neurotoxicity.

Authors: H. Loeffler-Wirth, M. Rade, A. Arakelyan, M. Kreuz, M. Loeffler, U. Koehl, K. Reiche, H. Binder

Date Published: 17th Oct 2022

Publication Type: Journal article

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imSAVAR - Immune safety avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies
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Creators: None

Submitter: Henry Löffler-Wirth

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imSAVAR - Immune safety avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies
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Creators: None

Submitter: Henry Löffler-Wirth

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