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. 2020 Jul 28;4(14):3252-3257.
doi: 10.1182/bloodadvances.2020002252.

Complement inhibition does not impair the clinical antiviral capabilities of virus-specific T-cell therapy

Jeremy D Rubinstein  1   2 , Xiang Zhu  3 , Carolyn Lutzko  1   3 , Tom Leemhuis  4 , Jose A Cancelas  1   3   4 , Sonata Jodele  1   2 , Catherine M Bollard  5   6 , Patrick J Hanley  5   6 , Stella M Davies  1   2 , Michael S Grimley  1   2 , Adam S Nelson  1   2
Affiliations

Complement inhibition does not impair the clinical antiviral capabilities of virus-specific T-cell therapy

Jeremy D Rubinstein et al. Blood Adv. .

Abstract

  1. The use of terminal complement blockade is compatible with virus-specific T-cell (VST) expansion and clinical effectiveness.

  2. VST and complement-blocking agent concurrent therapy may be safely used in patients with thrombotic microangiopathy and viral infections.

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Conflict of interest statement

Conflict-of-interest disclosure: S.J. and S.M.D. have a US provisional patent application pending, and have research support from Alexion. S.J. has received travel support from Omeros. C.M.B. has equity ownership in Mana Therapeutics, serves on the scientific advisory board and has filed patents that cover generation of virus-specific T cells, has stock ownership in Neximmune and Torque, and serves on the board of directors of Cabaletta Bio. P.J.H. is a cofounder of, and is on the board of directors of, Mana Therapeutics and has intellectual property related to virus-specific T cells. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Expansion of antiviral T cells correlated with viral load under the influence of complement blockade. (A-E) Peripheral blood mononuclear cells (PBMCs) were isolated from patients at the time of VST infusion and weekly for the first 4 weeks afterward. Interferon-γ ELISpot was performed on samples after stimulation with pools of overlapping viral peptides (pepmix) from the treated virus. Interferon-γ (IFN-γ)–secreting T cells at each time point were plotted with the corresponding viral polymerase chain reaction quantification at that time. The timing of complement blockade is indicated by the start of eculizumab (ecu), discontinuation of ecu, and the time of CH50 normalization. CH50 normalization is a marker that complement blockade is no longer occurring in blood. Each panel represents ELISpot assay performed on samples isolated from distinct individual patients. ADV, adenovirus; BKV, BK virus; SFC, spot-forming cell.
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