title: Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens.
abstract: The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8(+) cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. ehwarren@u.washington.edu
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Fujii
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.forename: Colette N
authors.initials: CN
authors.lastname: Chaney
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Mito
authors.forename: Keith R
authors.initials: KR
authors.lastname: Loeb
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Michele L
authors.initials: ML
authors.lastname: Brown
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Koo
authors.forename: Kellie V
authors.initials: KV
authors.lastname: Rosinski
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Aiko
authors.initials: A
authors.lastname: Matsubara
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D020405:Dermis / Q000166:cytology / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D005434:Flow Cytometry; D006086:Graft vs Host Disease; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007124:Immunoenzyme Techniques; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000628:therapy; D009364:Neoplasm Recurrence, Local; D013601:T-Lymphocytes / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D015778:Minor Histocompatibility Antigens