Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model

Qing Ma, Changqing Wang, Dan Jones, Kathryn E. Quintanilla, Dan Li, Yang Wang, Eric Wieder, Karen Clise-Dwyer, Gheath Alatrash, You Mj, Mark F. Munsell, Sijie Lu, Muzaffar H. Qazilbash, Jeffrey J. Molldrem

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 7288% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 318% 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.

Original languageEnglish
Pages (from-to)1056-1062
Number of pages7
JournalCytotherapy
Volume12
Issue number8
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint

Adoptive Transfer
Cytotoxic T-Lymphocytes
Heterografts
Acute Myeloid Leukemia
Leukemia
Bone Marrow
Myeloid Cells
Myeloblastin
Inbred NOD Mouse
SCID Mice
Phenotype
Peptides
Neoplasm Antigens
Dendritic Cells
Blood Vessels
Blood Cells
Tissue Donors
Antigens
Liver

Keywords

  • acute myeloid leukemia
  • adoptive therapy
  • cytotoxic T lymphocytes
  • NOD/SCID
  • PR1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Molecular Medicine

Cite this

Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model. / Ma, Qing; Wang, Changqing; Jones, Dan; Quintanilla, Kathryn E.; Li, Dan; Wang, Yang; Wieder, Eric; Clise-Dwyer, Karen; Alatrash, Gheath; Mj, You; Munsell, Mark F.; Lu, Sijie; Qazilbash, Muzaffar H.; Molldrem, Jeffrey J.

In: Cytotherapy, Vol. 12, No. 8, 01.12.2010, p. 1056-1062.

Research output: Contribution to journalArticle

Ma, Q, Wang, C, Jones, D, Quintanilla, KE, Li, D, Wang, Y, Wieder, E, Clise-Dwyer, K, Alatrash, G, Mj, Y, Munsell, MF, Lu, S, Qazilbash, MH & Molldrem, JJ 2010, 'Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model', Cytotherapy, vol. 12, no. 8, pp. 1056-1062. https://doi.org/10.3109/14653249.2010.506506
Ma, Qing ; Wang, Changqing ; Jones, Dan ; Quintanilla, Kathryn E. ; Li, Dan ; Wang, Yang ; Wieder, Eric ; Clise-Dwyer, Karen ; Alatrash, Gheath ; Mj, You ; Munsell, Mark F. ; Lu, Sijie ; Qazilbash, Muzaffar H. ; Molldrem, Jeffrey J. / Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model. In: Cytotherapy. 2010 ; Vol. 12, No. 8. pp. 1056-1062.
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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 7288{\%} blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 318{\%} 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.",
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AU - Ma, Qing

AU - Wang, Changqing

AU - Jones, Dan

AU - Quintanilla, Kathryn E.

AU - Li, Dan

AU - Wang, Yang

AU - Wieder, Eric

AU - Clise-Dwyer, Karen

AU - Alatrash, Gheath

AU - Mj, You

AU - Munsell, Mark F.

AU - Lu, Sijie

AU - Qazilbash, Muzaffar H.

AU - Molldrem, Jeffrey J.

PY - 2010/12/1

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N2 - 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 7288% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 318% 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.

AB - 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 7288% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 318% 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.

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