Opportunistic viral infections such as cytomegalovirus (CMV), remain a major threat to the health of immunocompromised patients, including recipients of allogeneic hematopoietic stem-cell transplantation (HSCT). The first-generation CliniMACS® device from Miltenyi Biotec® “captures” CMV-specific T cells secreting γ-IFN after 4 hours of virus-derived peptide stimulation and these effector cells have been successfully infused to control CMV infection. This approach tends to be labor-intensive and requires a facility operating in compliance with good manufacturing practice (GMP). The high cost associated with this T-cell production in such facilities limits patients getting access to promising immunotherapies. The next-generation CliniMACS Prodigy® device largely automates the manufacture of clinical grade T cells using a closed system that does not require a dedicated GMP facility (https://www.jove.com/video/52808/automated-cell-enrichment-cytomegalovirus-specific-t-cells-for). Here, we report the results for viral-specific T-cell products harvested from eight steady-state apheresis products obtained from CMV seropositive donors. These were processed within 12 hours of stimulation in an automated fashion on the Prodigy device (a closed, hands-free system). Gene expression and TCR (αβ) repertoire analysis of pre and post captured T cells revealed that they retain their heterogeneity suggesting that the process is not inadvertently enriching a sub-set population of T cells. There was an average of 0.07% γ-IFN CD4+ T cells (range 0.03–0.61%) before and 62.2% (range 14.7–91.4%) after capture and enrichment; and 0.43% (range 0.07–0.56%) and 89.36% (range 61.6–94.2%) γ-IFN CD8+ T cells respectively. This yielded an average of 3 × 105 CD3+γ-IFN+ T cells per run. These numbers are clinically appealing as studies have demonstrated that infusing just a few thousand CMV-specific T cells may be effective as therapy for recipients undergoing allogeneic HSCT. These data demonstrate that the automated production of viral antigen-specific T cells is feasible and will likely enable investigators to produce clinical-grade donor-derived T cells for add-back after allogeneic HSCT at multiple points-of-care, thus broadening the application of this promising immunotherapy.
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