title: Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model.
abstract: OBJECTIVE
  Tumor antigen-specific cytotoxic T lymphocytes (CTL) have been used in the treatment of human cancer, including leukemia. Several studies have established PR1 peptide, an HLA-A2.1-restricted peptide derived from proteinase 3 (P3), as a human leukemia-associated antigen. PR1-specific CTL elicited in vitro from healthy donors have been shown to lyse P3-expressing AML cells from patients. We investigated whether PR1-CTL can be adoptively transferred into NOD/SCID mice to eliminate human leukemia cells.
  
  
  METHODS
  PR1-CTL were generated in bulk culture from peripheral blood mononuclear cells (PBMC) stimulated with autologous dendritic cells. Human acute myeloid leukemia (AML) patient samples were injected and engrafted in murine bone marrow at 2 weeks post-transfer.
  
  
  RESULTS
  Following adoptive transfer, bone marrow aspirate from mice that received AML alone had 72-88% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 3-18% blasts in a hypocellular marrow. The PR1-CTL persisted in the bone marrow and liver and maintained a CD45RA⁻CD28+ effector phenotype.
  
  
  CONCLUSIONS
  We found that adoptive transfer of PR1-CTL generated in vitro is associated with reduced AML cells in NOD/SCID mice. PR1-CTL can migrate to the sites of disease and maintain their capacity to kill the AML cells. The surface phenotype of PR1-CTL was consistent with their trafficking pattern in both vascular and end-organ tissues.
authors.affiliation: Section of Transplantation Immunology, Department of Stem Cell Transplantation and Cellular Therapy, University of Texas, MD Anderson Cancer Center, Unit 900, 1515 Holcombe Boulevard, Houston, TX 77030, USA. qma@mdanderson.org
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Changqing
authors.initials: C
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Quintanilla
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Eric D
authors.initials: ED
authors.lastname: Wieder
authors.forename: Karen
authors.initials: K
authors.lastname: Clise-Dwyer
authors.forename: Gheath
authors.initials: G
authors.lastname: Alatrash
authors.forename: You
authors.initials: Y
authors.lastname: Mj
authors.forename: Mark F
authors.initials: MF
authors.lastname: Munsell
authors.forename: Sijie
authors.initials: S
authors.lastname: Lu
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Molldrem
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D001853:Bone Marrow / Q000254:growth & development / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D053146:Myeloblastin / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: D000951:Antigens, Neoplasm; D010446:Peptide Fragments; D053146:Myeloblastin