Long–term restoration of immunity against Epstein–Barr virus infection by adoptive transfer of gene–modified virus–specific T lymphocytes

Abstract

Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) offers safe and effective therapy for certain viral infections and could prove useful in the eradication of tumor cells. Whether or not the infused T cells persist for extended periods, retaining their ability to expand in response to antigenic stimulation, is not known. We now report long-term detection of gene-marked Epstein-Barr virus (EBV)-specific CTLs in immunocompromised patients at risk for the development of EBV lymphoproliferative disease. Infusions of CTLs not only restored cellular immune responses against EBV, but also established populations of CTL precursors that could respond to in vivo or ex vivo challenge with the virus for as long as 18 months. Our findings support wider use of antigen-specific CTLs in adoptive immunotherapy.

Absence of retroviral vector-mediated transformation of gene-modified T cells after long-term engraftment in mice

“…However, with the exception of gene-modified virus-specific T cells in patients, 31,32 there has not been long-term follow-up of recipients in human or animal systems in which genemodified T cells were demonstrated to persist for several years. To investigate the issue of potential transforming ability of retroviral vectors in T cells, we performed adoptive transfer in mice and determined the incidence of cancer formation over their entire lifespan.…”

In vitro methods for generating highly purified EBV associated tumor antigen-specific T cells by using solid phase T cell selection system for immunotherapy

“…Adoptive cell transfer (ACT) immunotherapy is based on the ex vivo selection of tumor-reactive lymphocytes, their activation and numerical expansion before reinfusion to the autologous tumor-bearing host. ACT immunotherapy has successfully prevented and treated PTLD occurring after hematopoietic stem cell and solid organ transplants (Rooney et al, 1995;Heslop et al, 1996;Rooney et al, 1998;Khanna et al, 1999;Gustafsson et al, 2000).…”

Epstein‐Barr virus (EBV) latent membrane protein‐1‐specific cytotoxic T lymphocytes targeting EBV‐carrying natural killer cell malignancies

“…There is increasing interest in immunotherapy for EBV-associated malignancies and adoptive transfer of in vitro activated EBV-specific CTL has proven effective for prevention and treatment of EBV-associated lymphoproliferative diseases after stem cell and organ transplants [9][10][11][12][13]. Extension of a similar strategy to other EBV-associated malignancies, such as HD [14] and NPC [15], has been reported to be efficacious in some patients.…”