Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation.

Blood
Kenneth P MicklethwaiteGianpietro Dotti

Abstract

Viral infections and leukemic relapse account for the majority of treatment failures in patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving allogeneic hematopoietic stem cell (HSC) or cord blood (CB) transplants. Adoptive transfer of virus-specific cytotoxic T lymphocytes (CTLs) provides protection against common viruses causing serious infections after HSC transplantation without concomitant graft-versus-host disease. We have now generated CTL lines from peripheral blood (PB) or CB units that recognize multiple common viruses and provide antileukemic activity by transgenic expression of a chimeric antigen receptor (CAR) targeting CD19 expressed on B-ALL. PB-derived CAR(+) CTLs produced interferon-gamma (IFNgamma) in response to cytomegalovirus-pp65, adenovirus-hexon, and Epstein-Barr virus pepmixes (from 205 +/- 104 to 1034 +/- 304 spot-forming cells [SFCs]/10(5) T cells) and lysed primary B-ALL blasts in (51)Cr-release assays (mean, 66% +/- 5% specific lysis; effector-target [E/T] ratio, 40:1) and the CD19(+) Raji cell line (mean, 78% +/- 17%) in contrast to nontransduced controls (8% +/- 8% and 3% +/- 2%). CB-derived CAR(+) CTLs showed similar antiviral and antitumor function and both PB and CB CAR(+) CTLs co...Continue Reading

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Citations

Feb 22, 2011·International Journal of Hematology·Anna MerloAntonio Rosato
Oct 2, 2013·Immunology Letters·Barbara Savoldo, Gianpietro Dotti
Mar 2, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Donald B KohnHelen E Heslop
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Dec 5, 2015·Expert Review of Hematology·Frédéric BaronArnon Nagler
Nov 14, 2012·Expert Review of Hematology·Panayotis KaloyannidisAnastasia Papadopoulou
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May 26, 2012·Blood·Miranda P DierselhuisEls Goulmy

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