Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens.
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.
Warren
Edus H
EH
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. ehwarren@u.washington.edu
Fujii
Nobuharu
N
Akatsuka
Yoshiki
Y
Chaney
Colette N
CN
Mito
Jeffrey K
JK
Loeb
Keith R
KR
Gooley
Ted A
TA
Brown
Michele L
ML
Koo
Kevin K W
KK
Rosinski
Kellie V
KV
Ogawa
Seishi
S
Matsubara
Aiko
A
Appelbaum
Frederick R
FR
Riddell
Stanley R
SR
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
D014408:Biomarkers, Tumor; D015778:Minor Histocompatibility Antigens