Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein-Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant

Cytotherapy. 2012 Jan;14(1):7-11. doi: 10.3109/14653249.2011.636963.

Abstract

Infections with a range of common community viruses remain a major cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation. T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenoviruses can safely prevent and infections with these three most common culprits, but the manufacture of individual T cell lines for each virus would be prohibitive in terms of time and cost. We have demonstrated that T cells specific for all three viruses can be manufactured in a single culture using monocytes and EBV-transformed B lymphoblastoid cell lines (LCLs), both transduced with an adenovirus vector expressing pp65 of CMV, as antigen-presenting cells. Trivirus-specific T cell lines produced from healthy stem cell donors could prevent and treat infections with all three viruses, not only in the designated recipient, but in unrelated, partially-HLA-matched third party recipients. We now provide the details and logistics of T cell manufacture.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / immunology*
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / transplantation
  • Cell Culture Techniques*
  • Cell Line, Transformed
  • Cell Proliferation
  • Cytomegalovirus / immunology*
  • Cytotoxicity, Immunologic
  • HLA Antigens / immunology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Phosphoproteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / transplantation
  • Transplantation, Homologous / adverse effects
  • Viral Matrix Proteins / immunology
  • Virus Diseases / etiology*
  • Virus Diseases / therapy

Substances

  • HLA Antigens
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa