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LMP1-specific cytotoxic T cells for the treatment of EBV-related post-transplantation lymphoproliferative disorders.

Abstract
Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) represent a promising treatment option for EBV-associated post-transplantation lymphoproliferative disorders (PTLD). However, production of EBV-CTLs is often complicated and expensive. In the present study, we sought to establish an easy-to-use and economical production protocol for EBV-CTLs. EBV-CTLs were generated using latent membrane protein 1 (LMP1) peptides based on a modified generation protocol of cytokine-induced killer (CIK) cells. After 2-week culture, cells were well expanded (median total cell number: 9.82 × 109; median expansion fold: 107.8) and the median EBV LMP1-specific CD8+ T cell number was 8.94 × 108 (median frequency: 6.7%). However, the EBV-CTL products, unlike CIK cells, did not exhibit NK-like anti-tumor activity. Furthermore, the clinical efficacy of EBV-CTLs was demonstrated with a successful treatment of PTLD on a compassionate use basis in a patient following haploidentical hematopoietic stem cell transplantation. This study indicates the safety and efficacy of EBV LMP1-specific CTLs generated based on a modified generation protocol of CIK cells. Further investigation in a well-designed clinical study is warranted.
AuthorsJian Hong, Jing Ni, Min Ruan, Mingzhen Yang, Qianggang Dong, Qingsheng Li
JournalInternational journal of hematology (Int J Hematol) Vol. 111 Issue 6 Pg. 851-857 (Jun 2020) ISSN: 1865-3774 [Electronic] Japan
PMID32162095 (Publication Type: Case Reports, Journal Article)
Chemical References
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Viral Matrix Proteins
Topics
  • Adolescent
  • Anemia, Aplastic (therapy)
  • Cytokine-Induced Killer Cells
  • Epstein-Barr Virus Infections (complications)
  • Female
  • Hematopoietic Stem Cell Transplantation (adverse effects)
  • Hemoglobinuria, Paroxysmal (therapy)
  • Herpesvirus 4, Human
  • Humans
  • Immunotherapy, Adoptive (methods)
  • Lymphoproliferative Disorders (etiology, therapy)
  • Syndrome
  • T-Lymphocytes, Cytotoxic
  • Treatment Outcome
  • Viral Matrix Proteins

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