Selection of adenovirus-specific and Epstein-Barr virus–specific T cells with major histocompatibility class I streptamers under Good Manufacturing Practice (GMP)–compliant conditions

Freimüller, Christine; Stemberger, Julia; Artwohl, Michaela; Germeroth, Lothar; Witt, Volker; Fischer, Gottfried; Tischer, Sabine; Knippertz, Ilka; Dörrie, Jan; Schaft, Niels; Lion, Thomas; Fritsch, Gerhard; Geyeregger, René

doi:10.1016/j.jcyt.2015.03.613

Cited by 19 publications

(11 citation statements)

References 53 publications

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“…These data confirm previous reports of cross-species detection between species B and species C adenoviruses of these two peptide epitopes by specific T cells and allowed us to use Ad11pGFP as a reporter virus to further analyze T cells specific for these two peptide epitopes (13,23). These data also confirm previous observations that expansion of LTDLGQNLLY-specific T cells is more uniform and efficient than the more variable expansion of KPYSGTAYNAL-specific T cells (25).…”

Section: Cross-species Recognition Of Adenoviral Peptide Epitopes Frosupporting

confidence: 90%

Measuring Antiviral Capacity of T Cell Responses to Adenovirus

Keib¹,

Mei

Čičin-Šain

et al. 2019

The Journal of Immunology

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Adenoviruses are a major cause of infectious mortality in children following allogeneic hematopoietic stem cell transplantation, with adoptive transfer of adenovirus-specific T cells being an effective therapeutic approach. We have previously shown that T cells specific for the peptide epitope LTDLGQNLLY were protective. In this study, we aimed to establish a viral dissemination assay to measure the antiviral capacity of T cells specific for this and other peptide epitopes in an infectious setting. We used replication-competent adenovirus 11 (Ad11pGFP) and adenovirus 5 containing adenovirus 35 fiber (Ad5F35GFP) viruses and T cells specific for HLA-A*01-restricted LTDLGQNLLY, HLA-B*07-restricted KPYSGTAYNAL, and HLA-A*02-restricted LLDQLIEEV peptide epitopes. T cells in PBMC from healthy donors were expanded with peptide and IL-2 or treated with IL-2 alone to serve as nonstimulated control cells, and then these expanded or nonstimulated CD8 + cells were purified and cocultured with autologous monocytes infected with adenovirus at low multiplicity of infection. After 3 d, the number of infected GFP + monocytes and, hence, viral dissemination was quantified by flow cytometry. T cells expanded with LTDLGQNLLY peptide from multiple HLA-A*01 + donors prevented adenovirus dissemination, and nonstimulated T cells did not prevent dissemination, thus, indicating that LTDLGQNLLY-specific T cells have high antiviral capacity. Similarly, expanded KPYSGTAYNAL-and LLDQLIEEV-specific T cells could prevent viral dissemination. However, the frequency of expanded T cells specific for these last two epitopes was variable between donors with consequent variable prevention of adenoviral dissemination. Taken together, we demonstrate that T cells specific for three peptide epitopes, from both structural and nonstructural proteins, can prevent adenoviral dissemination and provide a novel method to measure the antiviral capacity of adenovirus-specific T cell responses.

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Section: Cross-species Recognition Of Adenoviral Peptide Epitopes Frosupporting

confidence: 90%

Measuring Antiviral Capacity of T Cell Responses to Adenovirus

Keib¹,

Mei

Čičin-Šain

et al. 2019

The Journal of Immunology

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“…Its unique core Streptamer technology has been used to isolate viral-specific lymphocytes. 26 , 27 It has been reported recently that as a soluble and dissociable T-cell stimulation reagent, Expamer efficiently induces T cell receptor (TCR) signaling and efficiently activates T cells to support retroviral transduction and expansion. 26 , 28 Although Expamer-activated T cells remain to be functionally assessed in vivo , this soluble reagent is very attractive for large-scale clinical manufacturing as it can be easily added and removed from cell suspensions and provides consistent product purity to enable automation.…”

Section: Manufacturing Of Car-t Cellsmentioning

confidence: 99%

Clinical manufacturing of CAR T cells: foundation of a promising therapy

Wang

Rivière

2016

Molecular Therapy - Oncolytics

507

411

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The treatment of cancer patients with autologous T cells expressing a chimeric antigen receptor (CAR) is one of the most promising adoptive cellular therapy approaches. Reproducible manufacturing of high-quality, clinical-grade CAR-T cell products is a prerequisite for the wide application of this technology. Product quality needs to be built-in within every step of the manufacturing process. We summarize herein the requirements and logistics to be considered, as well as the state of the art manufacturing platforms available. CAR-T cell therapy may be on the verge of becoming standard of care for a few clinical indications. Yet, many challenges pertaining to manufacturing standardization and product characterization remain to be overcome in order to achieve broad usage and eventual commercialization of this therapeutic modality.

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“…However, an increase in purity was achieved by small-scale selection or simultaneous application of EBV- and AdV-streptamers. An IFN-γ response was seen in most of the products and cells were predominantly of the effector memory (CD62L − CD45RA − ) or central memory phenotype (CD62L + CD45RA − ), thus those cells are suitable for clinical use (175). …”

Section: Immunotherapy With Antiviral T Cells To Treat Infectious Commentioning

confidence: 99%

Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications

et al. 2016

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Allogeneic hematopoietic stem cell transplantation is associated with serious complications, and improvement of the overall clinical outcome of patients with hematological malignancies is necessary. During the last decades, posttransplant donor-derived adoptive cellular immunotherapeutic strategies have been progressively developed for the treatment of graft-versus-host disease (GvHD), infectious complications, and tumor relapses. To date, the common challenge of all these cell-based approaches is their implementation for clinical application. Establishing an appropriate manufacturing process, to guarantee safe and effective therapeutics with simultaneous consideration of economic requirements is one of the most critical hurdles. In this review, we will discuss the recent scientific findings, clinical experiences, and technological advances for cell processing toward the application of mesenchymal stromal cells as a therapy for treatment of severe GvHD, virus-specific T cells for targeting life-threating infections, and of chimeric antigen receptors-engineered T cells to treat relapsed leukemia.

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Selection of adenovirus-specific and Epstein-Barr virus–specific T cells with major histocompatibility class I streptamers under Good Manufacturing Practice (GMP)–compliant conditions

Cited by 19 publications

References 53 publications

Measuring Antiviral Capacity of T Cell Responses to Adenovirus

Measuring Antiviral Capacity of T Cell Responses to Adenovirus

Clinical manufacturing of CAR T cells: foundation of a promising therapy

Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications

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