Dataset Information

Large-scale expansion and characterization of CD3⁺ T-cells in the Quantum^® Cell Expansion System.

ABSTRACT:

Background

The rapid evolution of cell-based immunotherapies such as chimeric antigen receptor T-cells for treatment of hematological cancers has precipitated the need for a platform to expand these cells ex vivo in a safe, efficient, and reproducible manner. In the Quantum^® Cell Expansion System (Quantum system) we evaluated the expansion of T-cells from healthy donors in a functionally-closed environment that reduces time and resources needed to produce a therapeutic dose.

Methods

Mononuclear cells from leukapheresis products from 5 healthy donors were activated with anti-CD3/CD28 Dynabeads^® and expanded in the Quantum system for 8-9 days using xeno-free, serum-free medium and IL-2. Harvested cells were phenotyped by flow cytometry and evaluated for cytokine secretion by multiplex assays.

Results

From starting products of 30 or 85?×?10⁶ mononuclear cells, CD3⁺ T-cell populations expanded over 500-fold following stimulation to provide yields up to 25?×?10⁹ cells within 8 days. T-cell yields from all donors were similar in terms of harvest numbers, viability and doubling times. Functionality (secretion of IFN-?, IL-2 and TNF-?) was retained in harvested T-cells upon restimulation in vitro and T-cells displayed therapeutically-relevant less-differentiated phenotypes of naïve and central memory T-cells, with low expression of exhaustion markers LAG-3 and PD-1.

Conclusions

The Quantum system has been successfully used to produce large quantities of functional T-cells at clinical dosing scale and within a short timeframe. This platform could have wide applicability for autologous and allogeneic cellular immunotherapies for the treatment of cancer.

SUBMITTER: Coeshott C

PROVIDER: S-EPMC6686483 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Large-scale expansion and characterization of CD3<sup>+</sup> T-cells in the Quantum<sup>®</sup> Cell Expansion System.

Coeshott Claire C Vang Boah B Jones Mark M Nankervis Brian B

Journal of translational medicine 20190807 1

<h4>Background</h4>The rapid evolution of cell-based immunotherapies such as chimeric antigen receptor T-cells for treatment of hematological cancers has precipitated the need for a platform to expand these cells ex vivo in a safe, efficient, and reproducible manner. In the Quantum<sup>®</sup> Cell Expansion System (Quantum system) we evaluated the expansion of T-cells from healthy donors in a functionally-closed environment that reduces time and resources needed to produce a therapeutic dose.<h ...[more]

PMID: 31391068

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Project description:Background: Lymphocytic variant hypereosinophilic syndrome is characterized by marked over-production of eosinophilopoietic factor(s) by dysregulated T cells leading to eosinophil expansion. In most cases, these T cells are clonal and express a CD3-CD4+ phenotype. As this is a rare disorder, presenting manifestations, disease course, treatment responses, and outcome are not well-characterized. Materials and Methods: In this retrospective single-center observational study, we reviewed medical files of all patients with persistent hypereosinophilia seen between 1994 and 2019 in whom CD3-CD4+ T cells were detected. Data collection included clinical and biological findings at presentation, treatment responses, disease course, and serial CD3-CD4+ T cell counts. Results: Our cohort comprises 26 patients, including 2 with hypereosinophilia of undetermined significance. All 24 symptomatic patients had cutaneous lesions and/or angioedema, and fasciitis was present in several cases. The aberrant T cell subset represented 2% or less total lymphocytes in 11 subjects. TCR gene rearrangement patterns on whole blood were polyclonal in these cases, while they all had serum CCL17/TARC levels above 1,500 pg/ml. Disease manifestations were mild and did not require maintenance therapy in roughly one third of the cohort, while two thirds required long-term oral corticosteroids and/or second-line agents. Among these, interferon-alpha was the most effective treatment option with a response observed in 8/8 patients, one of whom was cured of disease. Treatment had to be interrupted in most cases however due to poor tolerance and/or development of secondary resistance. Anti-interleukin-5 antibodies reduced blood eosinophilia in 5/5 patients, but clinical responses were disappointing. A sub-group of 5 patients had severe treatment-refractory disease, and experienced significant disease- and treatment-related morbidity and mortality, including progression to T cell lymphoma in three. Conclusions: This retrospective longitudinal analysis of the largest monocentric cohort of CD3-CD4+ T cell associated lymphocytic variant hypereosinophilic syndrome published so far provides clinicians confronted with this rare disorder with relevant new data on patient presentation and outcome that should help tailor therapy and follow-up to different levels of disease severity. It highlights the need for novel therapeutic options, especially for the subset of patients with severe treatment-refractory disease. Future research efforts should be made toward understanding CD3-CD4+ T cell biology in order to develop new treatments that target primary pathogenic mechanisms.

Dataset Information

Large-scale expansion and characterization of CD3⁺ T-cells in the Quantum^® Cell Expansion System.

Background

Methods

Results

Conclusions

Publications

Large-scale expansion and characterization of CD3<sup>+</sup> T-cells in the Quantum<sup>®</sup> Cell Expansion System.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Large-scale expansion and characterization of CD3+ T-cells in the Quantum® Cell Expansion System.

Background

Methods

Results

Conclusions

Publications

Large-scale expansion and characterization of CD3<sup>+</sup> T-cells in the Quantum<sup>®</sup> Cell Expansion System.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Large-scale expansion and characterization of CD3⁺ T-cells in the Quantum^® Cell Expansion System.