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S. Vasileiou et al.
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Figure 5. Detection of respiratory virus-tar- geted (RSV)- and human metapneumovirus (hMPV)-specific T cells in the peripheral blood of hematopoietic stem cell transplant (HSCT) recipients. Peripheral blood mononuclear cells (PBMC) isolated from two HSCT recipients with three infections were tested for specificity against the infecting viruses, using IFNγ ELIspot as a readout. (A and B) Results from two patients with RSV- associated upper respiratory tract infection (URTI) which was controlled, coincident with a detectable rise in endogenous RSV-specif- ic T cells. (C) Clearance of an hMPV-lower respiratory tract infection (LRTI) with expan- sion of endogenous hMPV-specific T cells. ALC: absolute lymphocyte count.
peripheral blood of five allogeneic HSCT recipients with active RSV, hMPV and PIV-3 infections. Four of these patients successfully controlled the viruses within 1-5 weeks, coincident with an amplification of endogenous reactive T cells and subsequent return to baseline levels upon viral clearance, while one patient failed to mount an immune response against the infecting virus and has equally failed to clear the infection to date. These data suggests that the adoptive transfer of ex vivo-expanded cells should be clinically beneficial in patients whose own cellular immunity is lacking.
In conclusion, we have shown that it is feasible to rap- idly generate a single preparation of polyclonal multi-res- piratory (multi-R)-VST with specificities directed to Influenza, RSV, hMPV and PIV-3 in clinically relevant numbers using GMP-compliant manufacturing method-
ologies. These data provide the rationale for a future clin- ical trial of adoptively transferred multi-R-VST for the pre- vention or treatment of CARV infections in immunocom- promised patients.
Funding
This work was supported by the Flow Cytometry and Cell and Vector Production shared resources in the Dan L. Duncan Comprehensive Cancer Center (support grant P30 CA125123).
SV was funded in part by an educational grant from the Hellenic Foundation of Hematology. PL is supported by the American Society of Hematology Junior Faculty Scholar grant and the Leukemia Texas Research grant. J. F. V. is supported by a Mentored Research Scholars Grant in Applied and Clinical Research (grant number MRSG-14-197-01-LIB) from the American Cancer Society.
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haematologica | 2020; 105(1)