The time is now: moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care

Abstract

Adoptive immunotherapy-in particular, T-cell therapy-has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation. In this review, we briefly summarize the current methods for virus-specific T-cell isolation or selection and we report results from clinical trials that have used these techniques, focusing specifically on the strategies aimed to broaden the application of this technology.

Keywords: T cell; immunotherapy; stem cell transplantation; virus.

Figure 1

GMP-applicable approaches for the generation of virus-specific T cells. (A) In the classic ex vivo expansion, T cells are combined with APCs that have been transduced with either a viral vector or plasmids encoding the antigens of interest. The APCs are used to stimulate the T cells until cells of sufficient specificity and number have been expanded. (B) To prepare virus-specific T cells with the use of multimers, T cells are incubated with multimers that mimic the peptide:MHC binding of an APC. The T cells that bind the multimer are then isolated with the use of magnetic beads or fluorescence-activated cell sorting. (C) In the gamma-capture technique, T cells are activated use of the peptide of interest to stimulate the T cells. Once the T cells are stimulated, antibodies bind IFN-γ and the T cell, allowing the T cells to be isolated by magnetic selection. (D) To improve on the classic ex vivo expansion system, the rapid system utilizes the APCs present in the PBMC. The PBMCs are pulsed with overlapping peptides representing the viral antigens(s) of interest. APCs pulsed with the peptides then stimulate the T cells to grow. When coupled with a G-rex gas-permeable culture device, these CTL are ready 9–12 d after initiation.