Abstract:
BACKGROUND AIMS: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.
journal_name
Cytotherapyjournal_title
Cytotherapyauthors
Ma Q,Wang C,Jones D,Quintanilla KE,Li D,Wang Y,Wieder ED,Clise-Dwyer K,Alatrash G,Mj Y,Munsell MF,Lu S,Qazilbash MH,Molldrem JJdoi
10.3109/14653249.2010.506506subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1056-62issue
8eissn
1465-3249issn
1477-2566pii
S1465-3249(10)70474-6journal_volume
12pub_type
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