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S. Vasileiou et al.
vance of CARV-specific T cells in the control of viral infections in immunocompromised patients.
Discussion
In the present study, we explored the feasibility of target- ing multiple clinically problematic respiratory viruses using ex vivo expanded T cells. We have now shown that we can rapidly generate polyclonal, CD4+ and CD8+ T cells with specificities directed to a total of 12 antigens derived from four seasonal CARV [Influenza, RSV, hMPV and PIV-3] that are responsible for upper and lower respiratory tract infec- tions in the immunocompromised host. These broad spec-
trum VST, generated using GMP-compliant methodologies, were Th1-polarized, produced multiple effector cytokines upon stimulation, and killed virus-infected targets without auto- or allo-reactivity. Finally, the detection of reactive T- cell populations in the peripheral blood of allogeneic HSCT recipients who successfully cleared active CARV infections suggests the potential for clinical benefit following the adoptive transfer of such multi-R-VST.
Community-acquired respiratory virus-associated acute upper and lower RTI are a major public health problem with young children, the elderly and those with sup- pressed or compromised immune systems being the most vulnerable.1-3 These infections are associated with symp- toms including cough, dyspnea, and wheezing, and
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Figure 3. Multi-respiratory virus-targeted cells (multi-R-VST) are polyclonal and polyfunctional. (A) Dual IFNγ and TNFα production from CD3+ T cells as assessed by intracellular cytokine staining (ICS) in one representative donor. (B) Summary of results from nine donors screened [mean±Standard Error of Mean (SEM)]. (C) Cytokine profile of multi-R-VST as measured by multiplex bead array. (D) Assessment of the production of Granzyme B by ELIspot assay. Results are reported as SFC/2x105 input VST (mean±SEM, n=9).
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haematologica | 2020; 105(1)