title: Adoptive immunotherapy with CMV-specific cytotoxic T lymphocytes for stem cell transplant patients with refractory CMV infections.
abstract: Adoptive immunotherapy with cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) is an effective strategy for preventing and treating viral reactivation after allogeneic stem cell transplantation (SCT). We have shown previously that CMV CTL can be generated in 1 to 2 weeks by stimulating donor lymphocytes with peptide mixes derived from full-length pp65 and IE1. We conducted a multi-institutional study of CMV-specific CTL for patients with persistent or anti-viral-resistant CMV infections after allogeneic SCT, to determine the safety, feasibility, and immunologic effects of this approach. We were successful in stimulating CTL from 10/10 donors with pooled CMV overlapping peptide mixes. Five of the 7 subjects who met infusion criteria had new onset CMV-specific CTL activity detected within 4 to 6 weeks after infusion. Of the 2 subjects who did not have immunologic responses after infusion, 1 received CTL with a low viability after thawing, and the other patient received cyclosporine A and systemic corticosteroids at the time of the infusion, achieving only a low, transient increase (10%) in pp65-specific activity. There was no graft-versus-host disease attributable to these infusions. These findings indicate that the infusion of CTL stimulated over 1 to 2 weeks with overlapping CMV peptides can result in virus-specific immune reconstitution in SCT recipients, without exacerbations of graft-versus-host disease.
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Stem Cell Transplantation Program, Penn State Hershey Children's Hospital, Hershey, PA, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Cowan
authors.forename: Kimberly
authors.initials: K
authors.lastname: Dunham
authors.forename: Biljana
authors.initials: B
authors.lastname: Horn
authors.forename: Joseph
authors.initials: J
authors.lastname: McGuirk
authors.forename: Andrew
authors.initials: A
authors.lastname: Gilman
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Lucas
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007223:Infant; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult