Viral infections remain a major cause of morbidity and mortality post-transplant.
To address this issue, and with NHLBI-PACT support, we have made virus-specific T-cell
lines (VSTs) with activity against 5 common post-transplant viruses (EBV, CMV, Adv,
BK, HHV6), using a simplified 10-day. To date 48 clinical-grade multivirus (m)VSTs
have been generated. By exposing 30x10ˆ6 PBMCs to overlapping peptide libraries spanning
Adv (Hexon, Penton), CMV (pp65, IE1), EBV (LMP2, EBNA1, BZLF1), BK (Large T, VP1)
and HHV6 (U11, U14, U90) antigens we expanded a median of 35.7x10ˆ7 polyclonal cells
over 9-11 days. pVST specificity was dependent on the donor's prior viral exposure;
45/48 lines had Adv activity (Hexon: 470±71; Penton: 366±86 SFC/2x10ˆ5), 26/48 against
CMV (IE1: 356±157; pp65: 1048±446), 37/48 against EBV (LMP2: 137±76; EBNA1: 123±52;
BZLF1: 99±7), 28/48 against BK (Large T: 123±61; VP1: 208±89) and 29/48 against HHV6
(U90: 109±78; U11: 37±17; U14: 84±26). None of the lines reacted against recipient
cells. To date 11 allogeneic HSCT recipients have received 0.5-2x10ˆ7 pVSTs/m2 without
adverse events. Three patients were infused prophylactically while 8 were treated
for one or more active infections. A single infusion successfully controlled active
infections associated with all our targeted viruses: CMV (2 CR, 1 PR); EBV (5 CR);
Adv (1 CR); HHV6 (2 CR) and BK (5 CR, 1 PR, 1 NR). Of note, all 3 patients with BK
hemorrhagic cystitis had marked improvement/disappearance of hematuria post-mVSTs.
Our only “mixed” responder cleared EBV and HHV6 but not BK following the infusion
of a line that lacked specificity for this virus, likely reflecting the seronegative
status of the donor. Thus, infusion of mVSTs has been safe and clinically effective
against up to four simultaneous/sequential infections in a single HSCT recipient.
We are planning to assess the activity of “off the shelf” 3rd party pVSTs for broader
To read this article in full you will need to make a payment
© 2014 Published by Elsevier Inc.