Adoptive transfer and selective reconstitution of streptamer‐selected cytomegalovirus‐specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation

Abstract

Taken together, the streptamer technology offers the advantage of selecting virus-specific CD8+ T cells at GMP level for adoptive T-cell transfer, thus inducing long-lasting specific CD8+ T-cell responses without increasing the risk for graft-versus-host disease.

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

“…55 Given the variety of immune cells contained in the apheresis product, many strategies have been developed in order to rationally select graft effectors and provide designed adoptive immunotherapies, especially in the haploidentical stem cell transplant setting. [56][57][58] In this scenario, Schumm et al 59 recently introduced an innovative approach of graft manipulation, which consist in depleting the leukapheresis product of only TCR αβ + T cells and CD19 + B cells, thus retaining large numbers of crucial immune effectors such as TCR γδ + T cells, NK cells and DCs; this method has been safely tested in a cohort of children by Locatelli and colleagues. 60 Although G-CSF mobilization is known to alter phenotype and cytokine polarization of transplanted immune cells, very few data are available on the impact of plerixafor on allogeneic graft cell subsets, as it is not approved for administration in healthy donors yet.…”

Antiviral treatment of cytomegalovirus infection: an update

“…Other strategies use an in vitro stimulation of antigenpresenting cells with HCMV-specific proteins or peptides [29]. The streptamer technology has been used successfully for adoptive transfer of cytomegalovirus-specific CD8+ T-cells in two patients with recurrent high HCMV antigenemia after allogeneic stem cell transplantation [30].…”

Immunotherapy for viral and fungal infections

“…Using these streptamers and peptide pools covering several of the immunodominat viral antigenic epitopes, we have been able to generate T cell lines at high purity. 29,43 The technology can also be used to generate multivirus-specific T cell lines at high purity and with a good yield (unpublished results). An alternative technology developed in our labs is the selection of T cells directed against viral and fungal antigenic epitopes by stimulation with peptide mixes covering several relevant CMV-, EBV-, ADV-, Aspergillus fumigatus-and Candida albicans-specific T-cell epitopes followed by selection via the upregulated activation markers (for example, CD137, CD154 and so on).…”

“…21,28 New strategies of T-cell selection using antigen-induced T-cell stimulation and isolation by cytokine capture assay, streptamer technology 29 or via increased expression of activation markers has been developed. 9,10,30 In a recent study, this approach has been successfully applied to patients with chemorefractory CMV infection and disease.…”