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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Related Experiment Video

Updated: Jun 21, 2025

Expanding Cytotoxic T Lymphocytes from Umbilical Cord Blood that Target Cytomegalovirus, Epstein-Barr Virus, and Adenovirus
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EBV T-cell immunotherapy generated by peptide selection has enhanced effector functionality compared to LCL

Rachel S Cooper1,2, Catherine Sutherland3, Linda M Smith1

  • 1Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.

Frontiers in Immunology
|July 16, 2024
PubMed
Summary
This summary is machine-generated.

A new peptide-based method rapidly manufactures Epstein-Barr virus (EBV)-specific T cells (VST) for treating post-transplant lymphoproliferative disorders (PTLD). This virus-free approach yields superior T cell memory and broader antigen specificity compared to traditional methods.

Keywords:
Epstein-Barr virusT cellT cell receptorcell therapyimmunotherapylymphoblastoid cell linepeptidepotency

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Area of Science:

  • Immunotherapy
  • Virology
  • Cellular Biology

Background:

  • Adoptive immunotherapy using Epstein-Barr virus (EBV)-specific T cells offers a promising treatment for EBV-induced post-transplant lymphoproliferative disorders (PTLD).
  • Conventional manufacturing relies on EBV-transformed lymphoblastoid cell lines (LCLs), which is time-consuming, costly, and carries risks associated with live virus exposure.

Purpose of the Study:

  • To develop and characterize a novel peptide-based, virus-free manufacturing system for EBV-specific T cells (VST) for clinical applications.
  • To compare the efficacy and characteristics of peptide-derived VST with standard LCL-derived VST.

Main Methods:

  • Developed a peptide-based, virus-free, serum-free closed system for VST manufacturing.
  • Utilized multi-parameter flow cytometry, HLA-matched allogeneic cytotoxicity assays, and high-throughput T cell receptor-beta (TCRβ) sequencing for comprehensive characterization.
  • Assessed T cell populations, exhaustion markers, cytotoxic activity, cytokine production, and T cell receptor repertoires.

Main Results:

  • Peptide-derived VST exhibited an expanded central memory population and reduced expression of exhaustion markers compared to LCL-derived VST.
  • Both methods showed similar specific killing of EBV-infected targets, but peptide-derived VST displayed significantly higher antiviral cytokine and degranulation marker expression.
  • Peptide-derived VST demonstrated broader and enhanced specificity to EBV nuclear antigens (EBNAs) in both CD8+ and CD4+ T cell compartments.
  • The peptide-based approach allows for rapid manufacturing and significantly increased product yield.

Conclusions:

  • Peptide-based manufacturing offers a more efficient and potentially safer alternative for producing EBV-specific T cells for PTLD treatment.
  • The enhanced characteristics of peptide-derived VST, including improved memory and broader antigen targeting, may lead to superior clinical outcomes.
  • This novel approach streamlines VST production, making this immunotherapy more accessible for patients with relapsed or refractory PTLD.